1-53090709-T-G

Position:

• chr1-53090709-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The ENST00000371494.9(SLC1A7):​c.1129A>C​(p.Asn377His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC1A7 ENST00000371494.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.01

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.98

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A7	NM_006671.6	c.1129A>C	p.Asn377His	missense_variant	8/11	ENST00000371494.9	NP_006662.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A7	ENST00000371494.9	c.1129A>C	p.Asn377His	missense_variant	8/11	1	NM_006671.6	ENSP00000360549	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Jan 29, 2024

The c.1129A>C (p.N377H) alteration is located in exon 8 (coding exon 8) of the SLC1A7 gene. This alteration results from a A to C substitution at nucleotide position 1129, causing the asparagine (N) at amino acid position 377 to be replaced by a histidine (H). 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	0.99
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;T;.
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Benign	0.085	D
MetaRNN	Pathogenic	0.98	D;D;D
MetaSVM	Uncertain	0.39	D
MutationAssessor	Pathogenic	4.0	.;H;.
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.80	D
PROVEAN	Pathogenic	-4.5	.;D;.
REVEL	Pathogenic	0.69
Sift	Pathogenic	0.0	.;D;.
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.98
MutPred		0.96		.;Loss of stability (P = 0.1168);.;
MVP		0.88
MPC		0.43
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.88
gMVP		0.99

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-53556381;