1-53092567-C-T

Position:

• chr1-53092567-C-T

Variant summary

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

The NM_006671.6(SLC1A7):​c.1018G>A​(p.Ala340Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,176 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SLC1A7 NM_006671.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

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]

SLC1A7 (HGNC:):

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.1018G>A	p.Ala340Thr	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.1018G>A	p.Ala340Thr	missense_variant	7/11	1	NM_006671.6	ENSP00000360549.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461176 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 726920

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: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000680 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

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

Oct 03, 2024

The c.1018G>A (p.A340T) alteration is located in exon 7 (coding exon 7) of the SLC1A7 gene. This alteration results from a G to A substitution at nucleotide position 1018, causing the alanine (A) at amino acid position 340 to be replaced by a threonine (T). 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	0.80
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.10	T;T;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.60	D;D;D
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.6	.;L;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.7	.;D;.
REVEL	Uncertain	0.35
Sift	Uncertain	0.0050	.;D;.
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		0.46	.;P;.
Vest4		0.72
MVP		0.67
MPC		0.40
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.62
gMVP		0.80

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

Other links and lift over

dbSNP: rs371287501; hg19: chr1-53558239; COSMIC: COSV65201635; COSMIC: COSV65201635;