Genetic Variant NM_000550.3:c.1408+126C>T (chr9-12708269-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000550.3(TYRP1):c.1408+126C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0558 in 1,192,332 control chromosomes in the GnomAD database, including 2,114 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.056 ( 264 hom., cov: 32)

Exomes 𝑓: 0.056 ( 1850 hom. )

Consequence

TYRP1
NM_000550.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.811

Publications

3 publications found

Variant links:

Genes affected

TYRP1 (HGNC:12450): (tyrosinase related protein 1) This gene encodes a melanosomal enzyme that belongs to the tyrosinase family and plays an important role in the melanin biosynthetic pathway. Defects in this gene are the cause of rufous oculocutaneous albinism and oculocutaneous albinism type III. [provided by RefSeq, Mar 2009]

TYRP1 links:

LURAP1L-AS1 (HGNC:49761): (LURAP1L antisense RNA 1)

LURAP1L-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYRP1	NM_000550.3 link	c.1408+126C>T		intron_variant	Intron 7 of 7	ENST00000388918.10	NP_000541.1	P17643
LURAP1L-AS1	NR_125775.1 link	n.317-7643G>A		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000388918.10 link	c.1408+126C>T		intron_variant	Intron 7 of 7	1	NM_000550.3	ENSP00000373570.4		P17643

Frequencies

GnomAD3 genomes

AF:

0.0560

AC:

8505

AN:

151860

Hom.:

258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0563

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.0355

Gnomad ASJ

AF:

0.0758

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0114

Gnomad FIN

AF:

0.0842

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0623

Gnomad OTH

AF:

0.0551

GnomAD4 exome

AF:

0.0557

AC:

57948

AN:

1040354

Hom.:

1850

AF XY:

0.0542

AC XY:

28595

AN XY:

527702

show subpopulations

African (AFR)

AF:

0.0539

AC:

1295

AN:

24044

American (AMR)

AF:

0.0278

AC:

947

AN:

34022

Ashkenazi Jewish (ASJ)

AF:

0.0707

AC:

1529

AN:

21638

East Asian (EAS)

AF:

0.000117

AC:

AN:

34104

South Asian (SAS)

AF:

0.0157

AC:

1086

AN:

68986

European-Finnish (FIN)

AF:

0.0799

AC:

3895

AN:

48766

Middle Eastern (MID)

AF:

0.0487

AC:

218

AN:

4472

European-Non Finnish (NFE)

AF:

0.0613

AC:

46523

AN:

758564

Other (OTH)

AF:

0.0536

AC:

2451

AN:

45758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2786

5573

8359

11146

13932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1490

2980

4470

5960

7450

<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:

0.0562

AC:

8543

AN:

151978

Hom.:

264

Cov.:

AF XY:

0.0560

AC XY:

4158

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.0570

AC:

2366

AN:

41486

American (AMR)

AF:

0.0354

AC:

539

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.0758

AC:

263

AN:

3468

East Asian (EAS)

AF:

0.000194

AC:

AN:

5142

South Asian (SAS)

AF:

0.0114

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0842

AC:

893

AN:

10600

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0623

AC:

4234

AN:

67916

Other (OTH)

AF:

0.0540

AC:

114

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

417

834

1251

1668

2085

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0583

Hom.:

Bravo

AF:

0.0528

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.089

(source)

DANN

Benign

0.42

PhyloP100

-0.81

Mutation Taster

=100/0

polymorphism (auto)

(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

Computational scores

Splicing

Publications

Other links and lift over