NM_000372.5:c.819+1723A>G

Variant names:

• chr11-89180495-A-G
• rs621313
• NM_000372.5:c.819+1723A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000372.5(TYR):​c.819+1723A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 151,780 control chromosomes in the GnomAD database, including 28,325 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 0.59 (28325 hom., cov: 30)
• Consequence: TYR NM_000372.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220
• Publications: 20 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYR	NM_000372.5	c.819+1723A>G		intron_variant	Intron 1 of 4	ENST00000263321.6	NP_000363.1
TYR	XM_011542970.3	c.819+1723A>G		intron_variant	Intron 1 of 5		XP_011541272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYR	ENST00000263321.6	c.819+1723A>G		intron_variant	Intron 1 of 4	1	NM_000372.5	ENSP00000263321.4
TYR	ENST00000526139.1	n.880+1723A>G		intron_variant	Intron 1 of 2	1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88915 AN: 151660 Hom.: 28266 Cov.: 30

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.541

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.587 AC: 89045 AN: 151780 Hom.: 28325 Cov.: 30 AF XY: 0.584 AC XY: 43359 AN XY: 74182

African (AFR) AF: 0.856 AC: 35404 AN: 41380

American (AMR) AF: 0.508 AC: 7742 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1482 AN: 3468

East Asian (EAS) AF: 0.398 AC: 2045 AN: 5142

South Asian (SAS) AF: 0.469 AC: 2255 AN: 4808

European-Finnish (FIN) AF: 0.551 AC: 5787 AN: 10508

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32740 AN: 67904

Other (OTH) AF: 0.542 AC: 1144 AN: 2110

Alfa AF: 0.549 Hom.: 25301

Bravo AF: 0.592

Asia WGS AF: 0.487 AC: 1693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.34
DANN	Benign	0.48
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs621313; hg19: chr11-88913663;