Variant 3-126008826-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017836.4(SLC41A3):c.1160T>A(p.Leu387Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000258 in 1,614,214 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

SLC41A3
NM_017836.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.05

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC41A3	NM_017836.4 linkuse as main transcript	c.1160T>A	p.Leu387Gln	missense_variant	10/11	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.1160T>A	p.Leu387Gln	missense_variant	10/11	1	NM_017836.4	ENSP00000353533.4		Q96GZ6-9

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000187

AC:

AN:

251124

Hom.:

AF XY:

0.000206

AC XY:

AN XY:

135752

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000397

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000268

AC:

392

AN:

1461850

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

195

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000347

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.000164

AC:

AN:

152364

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000145

Hom.:

Bravo

AF:

0.000155

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000206

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2022

The c.1160T>A (p.L387Q) alteration is located in exon 10 (coding exon 9) of the SLC41A3 gene. This alteration results from a T to A substitution at nucleotide position 1160, causing the leucine (L) at amino acid position 387 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

.;.;.;T;.

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.99

D;D;D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.72

D;D;D;D;D

MetaSVM

Benign

-0.53

MutationAssessor

Pathogenic

3.2

M;.;.;M;.

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-5.7

D;D;D;D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.0010

D;D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D

Polyphen

1.0

.;D;D;D;.

Vest4

0.92

MVP

0.75

MPC

0.66

ClinPred

0.90

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.89

gMVP

0.65

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