rs494620

chr6-31870936-G-Achr6-31870936-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_025257.3(SLC44A4):c.813C>T(p.Tyr271=) 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
SLC44A4	NM_025257.3	c.813C>T	p.Tyr271=	synonymous_variant	10/21	ENST00000229729.11
SLC44A4	NM_001178044.2	c.687C>T	p.Tyr229=	synonymous_variant	9/20
SLC44A4	NM_001178045.2	c.585C>T	p.Tyr195=	synonymous_variant	10/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC44A4	ENST00000229729.11	c.813C>T	p.Tyr271=	synonymous_variant	10/21	1	NM_025257.3	P1

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

GnomAD3 exomes AF: 0.437 AC: 107556 AN: 245914 Hom.: 24388 AF XY: 0.438 AC XY: 58645 AN XY: 134016

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 SAS exome AF: 0.409

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

Gnomad4 AFR exome AF: 0.427

Gnomad4 AMR exome AF: 0.489

Gnomad4 ASJ exome AF: 0.646

Gnomad4 EAS exome AF: 0.515

Gnomad4 SAS exome AF: 0.414

Gnomad4 FIN exome AF: 0.341

Gnomad4 NFE exome AF: 0.396

Gnomad4 OTH exome AF: 0.409

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

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.450

Alfa AF: 0.434 Hom.: 21529

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

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Hearing loss, autosomal dominant 72 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	0.99
Dann	Benign	0.72

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

LitVar

Other links and lift over

dbSNP: rs494620; hg19: chr6-31838713; COSMIC: COSV57666908; COSMIC: COSV57666908;