rs74360232

Positions:

chr6-73600377-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_012434.5(SLC17A5):c.1324G>A(p.Val442Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000691 in 1,613,950 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00054 ( 2 hom. )

Consequence

SLC17A5
NM_012434.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:10

Conservation

PhyloP100: 2.38

Variant links:

Genes affected

SLC17A5 (HGNC:10933): (solute carrier family 17 member 5) This gene encodes a membrane transporter that exports free sialic acids that have been cleaved off of cell surface lipids and proteins from lysosomes. Mutations in this gene cause sialic acid storage diseases, including infantile sialic acid storage disorder and and Salla disease, an adult form. [provided by RefSeq, Jul 2008]

SLC17A5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013000339).

BP6

Variant 6-73600377-C-T is Benign according to our data. Variant chr6-73600377-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 235209.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1, Benign=3}. Variant chr6-73600377-C-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC17A5	NM_012434.5 linkuse as main transcript	c.1324G>A	p.Val442Ile	missense_variant	10/11	ENST00000355773.6	NP_036566.1	Q9NRA2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC17A5	ENST00000355773.6 linkuse as main transcript	c.1324G>A	p.Val442Ile	missense_variant	10/11	1	NM_012434.5	ENSP00000348019.5		Q9NRA2-1

Frequencies

GnomAD3 genomes

AF:

0.00215

AC:

327

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00589

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00769

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00113

AC:

283

AN:

251406

Hom.:

AF XY:

0.00101

AC XY:

137

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00609

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00685

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000264

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000536

AC:

783

AN:

1461736

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

352

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.00633

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00358

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000224

Gnomad4 OTH exome

AF:

0.00222

GnomAD4 genome

AF:

0.00218

AC:

332

AN:

152214

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

160

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00602

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00751

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00100

Hom.:

Bravo

AF:

0.00239

ESP6500AA

AF:

0.00635

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00130

AC:

158

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:10

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2023	SLC17A5: BP4 -
Uncertain significance, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 26, 2015	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Salla disease

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Jan 11, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Aug 28, 2015

- -

Sialic acid storage disease, severe infantile type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

SLC17A5-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 26, 2019

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

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.46

DEOGEN2

Benign

0.16

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.45

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.71

M_CAP

Benign

0.0085

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.010

REVEL

Benign

0.053

Sift

Benign

0.48

Sift4G

Benign

0.93

Polyphen

0.012

Vest4

0.24

MVP

0.43

MPC

0.15

ClinPred

0.0068

GERP RS

2.5

Varity_R

0.017

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over