chr11-89191217-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000372.5(TYR):c.835T>C(p.Leu279Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,613,386 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 14 hom., cov: 32)

Exomes 𝑓: 0.00075 ( 8 hom. )

Consequence

TYR
NM_000372.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.58

Publications

4 publications found

Variant links:

Genes affected

TYR (HGNC:12442): (tyrosinase) The enzyme encoded by this gene catalyzes the first 2 steps, and at least 1 subsequent step, in the conversion of tyrosine to melanin. The enzyme has both tyrosine hydroxylase and dopa oxidase catalytic activities, and requires copper for function. Mutations in this gene result in oculocutaneous albinism, and nonpathologic polymorphisms result in skin pigmentation variation. The human genome contains a pseudogene similar to the 3' half of this gene. [provided by RefSeq, Oct 2008]

TYR Gene-Disease associations (from GenCC):

oculocutaneous albinism type 1
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
oculocutaneous albinism type 1A
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
Waardenburg syndrome type 2
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
minimal pigment oculocutaneous albinism type 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
oculocutaneous albinism type 1B
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
temperature-sensitive oculocutaneous albinism type 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TYR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 11-89191217-T-C is Benign according to our data. Variant chr11-89191217-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 437173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.58 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00775 (1179/152134) while in subpopulation AFR AF = 0.0262 (1086/41518). AF 95% confidence interval is 0.0249. There are 14 homozygotes in GnomAd4. There are 565 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 14 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYR	NM_000372.5 link	c.835T>C	p.Leu279Leu	synonymous_variant	Exon 2 of 5	ENST00000263321.6	NP_000363.1	P14679-1L8B082
TYR	XM_011542970.3 link	c.835T>C	p.Leu279Leu	synonymous_variant	Exon 2 of 6		XP_011541272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYR	ENST00000263321.6 link	c.835T>C	p.Leu279Leu	synonymous_variant	Exon 2 of 5	1	NM_000372.5	ENSP00000263321.4		P14679-1
TYR	ENST00000526139.1 link	n.896T>C		non_coding_transcript_exon_variant	Exon 2 of 3	1

Frequencies

GnomAD3 genomes

AF:

0.00774

AC:

1176

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0262

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00479

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00207

AC:

519

AN:

251122

AF XY:

0.00156

show subpopulations

Gnomad AFR exome

AF:

0.0263

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000753

AC:

1100

AN:

1461252

Hom.:

Cov.:

AF XY:

0.000681

AC XY:

495

AN XY:

726928

show subpopulations

African (AFR)

AF:

0.0244

AC:

817

AN:

33438

American (AMR)

AF:

0.00220

AC:

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000928

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.000868

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000648

AC:

AN:

1111616

Other (OTH)

AF:

0.00159

AC:

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

112

169

225

281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00775

AC:

1179

AN:

152134

Hom.:

Cov.:

AF XY:

0.00760

AC XY:

565

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0262

AC:

1086

AN:

41518

American (AMR)

AF:

0.00479

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

67998

Other (OTH)

AF:

0.00473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

121

182

242

303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00461

Hom.:

Bravo

AF:

0.00948

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 31, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 10, 2015

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oculocutaneous albinism

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

TYR-related disorder

Benign:1

May 22, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.79

(source)

DANN

Benign

0.62

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over