chr19-14956678-C-A

Position:

• chr19-14956678-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005071.3(SLC1A6):​c.967G>T​(p.Ala323Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC1A6 NM_005071.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.84

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42057842).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A6	NM_005071.3	c.967G>T	p.Ala323Ser	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	c.967G>T	p.Ala323Ser	missense_variant	7/10	2	NM_005071.3	ENSP00000472133.2
SLC1A6	ENST00000221742.7	c.967G>T	p.Ala323Ser	missense_variant	6/9	1		ENSP00000221742.3
SLC1A6	ENST00000600144.5	c.936-2349G>T		intron_variant		1		ENSP00000471038.1
SLC1A6	ENST00000430939.6	c.775G>T	p.Ala259Ser	missense_variant	6/9	2		ENSP00000409386.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

The c.967G>T (p.A323S) alteration is located in exon 6 (coding exon 6) of the SLC1A6 gene. This alteration results from a G to T substitution at nucleotide position 967, causing the alanine (A) at amino acid position 323 to be replaced by a serine (S). 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	Benign	0.15
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.053	T;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.1	.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Uncertain	0.30
Sift	Uncertain	0.027	D;D
Sift4G	Uncertain	0.059	T;T
Polyphen		0.96	D;P
Vest4		0.50
MutPred		0.65		.;Gain of glycosylation at A323 (P = 0.0037);
MVP		0.69
MPC		0.44
ClinPred		0.96	D
GERP RS		4.0
Varity_R		0.27
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-15067490;