1-53088112-C-T

Position:

• chr1-53088112-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006671.6(SLC1A7):​c.1580G>A​(p.Cys527Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC1A7 NM_006671.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.61

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17434475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A7	NM_006671.6	c.1580G>A	p.Cys527Tyr	missense_variant	11/11	ENST00000371494.9	NP_006662.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A7	ENST00000371494.9	c.1580G>A	p.Cys527Tyr	missense_variant	11/11	1	NM_006671.6	ENSP00000360549	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.85e-7 AC: 1 AN: 1459912 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726084

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Apr 15, 2024

The c.1580G>A (p.C527Y) alteration is located in exon 11 (coding exon 11) of the SLC1A7 gene. This alteration results from a G to A substitution at nucleotide position 1580, causing the cysteine (C) at amino acid position 527 to be replaced by a tyrosine (Y). 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	0.068
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.0025
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;.
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.3	N;.
REVEL	Benign	0.19
Sift	Benign	0.25	T;.
Sift4G	Benign	0.18	T;T
Polyphen		0.068	B;.
Vest4		0.23
MutPred		0.57		Loss of disorder (P = 0.0892);.;
MVP		0.44
MPC		0.14
ClinPred		0.79	D
GERP RS		4.8
Varity_R		0.23
gMVP		0.52

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: chr1-53553784;