rs494620

Variant names:

• chr6-31870936-G-A
• rs494620
• NM_025257.3:c.813C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31870936-G-A
• chr6-31870936-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_025257.3(SLC44A4):​c.813C>T​(p.Tyr271Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,612,452 control chromosomes in the GnomAD database, including 138,800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (13732 hom., cov: 31)
  • Exomes 𝑓: 0.41 (125068 hom.)
• Consequence: SLC44A4 NM_025257.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.18
• Publications: 79 publications found

Genes affected

SLC44A4 (HGNC:13941): (solute carrier family 44 member 4) The protein encoded by this gene may be a sodium-dependent transmembrane transport protein involved in the uptake of choline by cholinergic neurons. Defects in this gene can cause sialidosis, a lysosomal storage disease. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

SLC44A4 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal dominant 72

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 6-31870936-G-A is Benign according to our data. Variant chr6-31870936-G-A is described in ClinVar as Benign. ClinVar VariationId is 1279733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.18 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC44A4	NM_025257.3	c.813C>T	p.Tyr271Tyr	synonymous_variant	Exon 10 of 21	ENST00000229729.11	NP_079533.2
SLC44A4	NM_001178044.2	c.687C>T	p.Tyr229Tyr	synonymous_variant	Exon 9 of 20		NP_001171515.1
SLC44A4	NM_001178045.2	c.585C>T	p.Tyr195Tyr	synonymous_variant	Exon 10 of 21		NP_001171516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC44A4	ENST00000229729.11	c.813C>T	p.Tyr271Tyr	synonymous_variant	Exon 10 of 21	1	NM_025257.3	ENSP00000229729.6
SLC44A4	ENST00000414427.1	c.686+378C>T		intron_variant	Intron 9 of 12	5		ENSP00000398901.1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63940 AN: 151796 Hom.: 13729 Cov.: 31

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.453

GnomAD2 exomes AF: 0.437 AC: 107556 AN: 245914 AF XY: 0.438

Gnomad AFR exome AF: 0.421

Gnomad AMR exome AF: 0.491

Gnomad ASJ exome AF: 0.653

Gnomad EAS exome AF: 0.440

Gnomad FIN exome AF: 0.352

Gnomad NFE exome AF: 0.427

Gnomad OTH exome AF: 0.448

GnomAD4 exome AF: 0.408 AC: 595644 AN: 1460536 Hom.: 125068 Cov.: 63 AF XY: 0.411 AC XY: 298745 AN XY: 726588

African (AFR) AF: 0.427 AC: 14308 AN: 33480

American (AMR) AF: 0.489 AC: 21847 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 16889 AN: 26132

East Asian (EAS) AF: 0.515 AC: 20444 AN: 39696

South Asian (SAS) AF: 0.414 AC: 35724 AN: 86232

European-Finnish (FIN) AF: 0.341 AC: 17868 AN: 52346

Middle Eastern (MID) AF: 0.555 AC: 3199 AN: 5766

European-Non Finnish (NFE) AF: 0.396 AC: 440667 AN: 1111856

Other (OTH) AF: 0.409 AC: 24698 AN: 60364

GnomAD4 genome AF: 0.421 AC: 63978 AN: 151916 Hom.: 13732 Cov.: 31 AF XY: 0.421 AC XY: 31263 AN XY: 74242

African (AFR) AF: 0.423 AC: 17498 AN: 41398

American (AMR) AF: 0.456 AC: 6956 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2244 AN: 3470

East Asian (EAS) AF: 0.434 AC: 2232 AN: 5146

South Asian (SAS) AF: 0.405 AC: 1953 AN: 4818

European-Finnish (FIN) AF: 0.344 AC: 3636 AN: 10564

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 27964 AN: 67956

Other (OTH) AF: 0.450 AC: 949 AN: 2108

Alfa AF: 0.430 Hom.: 33714

Bravo AF: 0.432

Asia WGS AF: 0.389 AC: 1358 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hearing loss, autosomal dominant 72 Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.99
DANN	Benign	0.72
PhyloP100		-1.2
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: rs494620; hg19: chr6-31838713; COSMIC: COSV57666908; COSMIC: COSV57666908;