Variant 19-14956488-C-G 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.1157G>C(p.Gly386Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000007 in 1,428,728 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SLC1A6
NM_005071.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.94

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.1157G>C	p.Gly386Ala	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.1157G>C	p.Gly386Ala	missense_variant	7/10	2	NM_005071.3	ENSP00000472133	P1	P48664-1
SLC1A6	ENST00000221742.7 linkuse as main transcript	c.1157G>C	p.Gly386Ala	missense_variant	6/9	1		ENSP00000221742	P1	P48664-1
SLC1A6	ENST00000600144.5 linkuse as main transcript	c.936-2159G>C		intron_variant		1		ENSP00000471038
SLC1A6	ENST00000430939.6 linkuse as main transcript	c.965G>C	p.Gly322Ala	missense_variant	6/9	2		ENSP00000409386

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000443

AC:

AN:

225480

Hom.:

AF XY:

0.00

AC XY:

AN XY:

120632

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000312

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.00e-7

AC:

AN:

1428728

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706714

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000238

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 10, 2023

The c.1157G>C (p.G386A) alteration is located in exon 6 (coding exon 6) of the SLC1A6 gene. This alteration results from a G to C substitution at nucleotide position 1157, causing the glycine (G) at amino acid position 386 to be replaced by an alanine (A). 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

0.51

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.093

T;D

Eigen

Benign

0.062

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D

M_CAP

Benign

0.049

MetaRNN

Uncertain

0.68

D;D

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.2

.;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.26

Sift

Benign

0.38

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.77

P;B

Vest4

0.89

MutPred

0.75

.;Gain of glycosylation at T383 (P = 0.1096);

MVP

0.46

MPC

1.3

ClinPred

0.63

GERP RS

3.8

Varity_R

0.33

gMVP

0.95

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