Variant 19-14956609-C-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_005071.3(SLC1A6):c.1036G>A(p.Val346Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000601 in 1,613,756 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

SLC1A6
NM_005071.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.82

Variant links:

Genes affected

SLC1A6 (HGNC:10944): (solute carrier family 1 member 6) Predicted to enable high-affinity glutamate transmembrane transporter activity. Involved in neurotransmitter uptake. Located in intermediate filament cytoskeleton and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC1A6 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
SLC1A6	NM_005071.3 linkuse as main transcript	c.1036G>A	p.Val346Ile	missense_variant	7/10	ENST00000594383.2	NP_005062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A6	ENST00000594383.2 linkuse as main transcript	c.1036G>A	p.Val346Ile	missense_variant	7/10	2	NM_005071.3	ENSP00000472133	P1	P48664-1
SLC1A6	ENST00000221742.7 linkuse as main transcript	c.1036G>A	p.Val346Ile	missense_variant	6/9	1		ENSP00000221742	P1	P48664-1
SLC1A6	ENST00000600144.5 linkuse as main transcript	c.936-2280G>A		intron_variant		1		ENSP00000471038
SLC1A6	ENST00000430939.6 linkuse as main transcript	c.844G>A	p.Val282Ile	missense_variant	6/9	2		ENSP00000409386

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251304

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000636

AC:

AN:

1461734

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000719

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152022

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000564

Hom.:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Apr 25, 2023

The c.1036G>A (p.V346I) alteration is located in exon 6 (coding exon 6) of the SLC1A6 gene. This alteration results from a G to A substitution at nucleotide position 1036, causing the valine (V) at amino acid position 346 to be replaced by an isoleucine (I). 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

0.39

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.053

T;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

D;D

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.54

D;D

MetaSVM

Uncertain

-0.25

MutationAssessor

Uncertain

2.7

.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.86

N;N

REVEL

Benign

0.28

Sift

Uncertain

0.016

D;D

Sift4G

Uncertain

0.027

D;D

Polyphen

1.0

D;D

Vest4

0.57

MutPred

0.63

.;Loss of catalytic residue at V346 (P = 0.0288);

MVP

0.35

MPC

0.38

ClinPred

0.44

GERP RS

2.9

Varity_R

0.19

gMVP

0.77

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