1-53092709-C-A

Position:

• chr1-53092709-C-A

Variant summary

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

The ENST00000371494.9(SLC1A7):​c.876G>T​(p.Lys292Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SLC1A7 ENST00000371494.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.515

Genes affected

SLC1A7 (HGNC:10945): (solute carrier family 1 member 7) Predicted to enable anion transmembrane transporter activity. Involved in neurotransmitter reuptake. Predicted to be located in plasma membrane. Predicted to be active in glutamatergic synapse. Predicted to be integral component of postsynaptic membrane and integral component of presynaptic membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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
SLC1A7	NM_006671.6	c.876G>T	p.Lys292Asn	missense_variant	7/11	ENST00000371494.9	NP_006662.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A7	ENST00000371494.9	c.876G>T	p.Lys292Asn	missense_variant	7/11	1	NM_006671.6	ENSP00000360549	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461824 Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2 AN XY: 727218

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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 26, 2023

The c.876G>T (p.K292N) alteration is located in exon 7 (coding exon 7) of the SLC1A7 gene. This alteration results from a G to T substitution at nucleotide position 876, causing the lysine (K) at amino acid position 292 to be replaced by an asparagine (N). 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	Pathogenic	0.70
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	T;T;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.57	D;D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.3	.;L;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.0	.;D;.
REVEL	Benign	0.13
Sift	Benign	0.031	.;D;.
Sift4G	Benign	0.10	T;T;T
Polyphen		0.16	.;B;.
Vest4		0.64
MutPred		0.57		.;Loss of ubiquitination at K292 (P = 0.0326);Loss of ubiquitination at K292 (P = 0.0326);
MVP		0.69
MPC		0.38
ClinPred		0.97	D
GERP RS		4.0
Varity_R		0.49
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr1-53558381;