Variant 3-126015503-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017836.4(SLC41A3):c.961G>A(p.Val321Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000165 in 1,614,166 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 2 hom. )

Consequence

SLC41A3
NM_017836.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.818

Variant links:

Genes affected

SLC41A3 (HGNC:31046): (solute carrier family 41 member 3) Predicted to enable cation transmembrane transporter activity. Predicted to be involved in cation transmembrane transport. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC41A3 links:

SLC41A3 (HGNC:):

SLC41A3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03284958).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC41A3	NM_017836.4 linkuse as main transcript	c.961G>A	p.Val321Ile	missense_variant	8/11	ENST00000360370.9	NP_060306.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC41A3	ENST00000360370.9 linkuse as main transcript	c.961G>A	p.Val321Ile	missense_variant	8/11	1	NM_017836.4	ENSP00000353533.4		Q96GZ6-9

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000597

AC:

AN:

251398

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000174

AC:

255

AN:

1461830

Hom.:

Cov.:

AF XY:

0.000165

AC XY:

120

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000301

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000200

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00781

Hom.:

817

Bravo

AF:

0.0000604

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.65

CADD

Benign

5.5

DANN

Benign

0.92

DEOGEN2

Benign

0.019

.;.;.;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.82

T;T;T;T;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.033

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.38

N;.;.;N;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.45

N;N;N;N;N

REVEL

Benign

0.018

Sift

Benign

0.17

T;T;T;T;T

Sift4G

Benign

0.29

T;T;T;T;T

Polyphen

0.074, 0.021, 0.30

.;B;B;B;.

Vest4

0.17

MVP

0.067

MPC

0.15

ClinPred

0.016

GERP RS

-0.34

Varity_R

0.011

gMVP

0.33

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