rs16883930

Positions:

chr6-73621896-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012434.5(SLC17A5):c.886G>A(p.Val296Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0117 in 1,613,866 control chromosomes in the GnomAD database, including 463 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 57 hom., cov: 33)

Exomes 𝑓: 0.011 ( 406 hom. )

Consequence

SLC17A5
NM_012434.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 5.70

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022813678).

BP6

Variant 6-73621896-C-T is Benign according to our data. Variant chr6-73621896-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 198552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-73621896-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC17A5	NM_012434.5 linkuse as main transcript	c.886G>A	p.Val296Ile	missense_variant	7/11	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.886G>A	p.Val296Ile	missense_variant	7/11	1	NM_012434.5	ENSP00000348019.5		Q9NRA2-1

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

2279

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00721

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0415

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.0176

Gnomad FIN

AF:

0.0128

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00628

Gnomad OTH

AF:

0.0292

GnomAD3 exomes

AF:

0.0236

AC:

5939

AN:

251438

Hom.:

205

AF XY:

0.0214

AC XY:

2914

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00615

Gnomad AMR exome

AF:

0.0554

Gnomad ASJ exome

AF:

0.0206

Gnomad EAS exome

AF:

0.109

Gnomad SAS exome

AF:

0.0182

Gnomad FIN exome

AF:

0.0131

Gnomad NFE exome

AF:

0.00627

Gnomad OTH exome

AF:

0.0254

GnomAD4 exome

AF:

0.0114

AC:

16613

AN:

1461602

Hom.:

406

Cov.:

AF XY:

0.0112

AC XY:

8111

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.00633

Gnomad4 AMR exome

AF:

0.0543

Gnomad4 ASJ exome

AF:

0.0218

Gnomad4 EAS exome

AF:

0.0993

Gnomad4 SAS exome

AF:

0.0186

Gnomad4 FIN exome

AF:

0.0119

Gnomad4 NFE exome

AF:

0.00523

Gnomad4 OTH exome

AF:

0.0195

GnomAD4 genome

AF:

0.0150

AC:

2281

AN:

152264

Hom.:

Cov.:

AF XY:

0.0159

AC XY:

1180

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00719

Gnomad4 AMR

AF:

0.0416

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.109

Gnomad4 SAS

AF:

0.0176

Gnomad4 FIN

AF:

0.0128

Gnomad4 NFE

AF:

0.00628

Gnomad4 OTH

AF:

0.0293

Alfa

AF:

0.0108

Hom.:

Bravo

AF:

0.0176

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.00590

AC:

ESP6500EA

AF:

0.00709

AC:

ExAC

AF:

0.0221

AC:

2682

Asia WGS

AF:

0.0740

AC:

257

AN:

3478

EpiCase

AF:

0.00747

EpiControl

AF:

0.00747

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	curation	SIB Swiss Institute of Bioinformatics	May 31, 2018	This variant is interpreted as a Benign - Stand Alone. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 12, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 14, 2014	- -

Salla disease

Benign:3

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Sialic acid storage disease, severe infantile type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

Eigen

Benign

0.095

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.84

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.41

REVEL

Benign

0.20

Sift

Benign

0.38

Sift4G

Benign

0.58

Polyphen

0.58

Vest4

0.14

MPC

0.16

ClinPred

0.017

GERP RS

5.9

Varity_R

0.13

gMVP

0.26

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

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