NM_004172.5:c.319+5876G>T

Variant names:

• chr5-36635463-G-T
• rs1366632
• NM_004172.5:c.319+5876G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004172.5(SLC1A3):​c.319+5876G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 152,028 control chromosomes in the GnomAD database, including 20,550 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (20550 hom., cov: 32)
• Consequence: SLC1A3 NM_004172.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 9 publications found

Genes affected

SLC1A3 (HGNC:10941): (solute carrier family 1 member 3) This gene encodes a member of a member of a high affinity glutamate transporter family. This gene functions in the termination of excitatory neurotransmission in central nervous system. Mutations are associated with episodic ataxia, Type 6. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2014]

SLC1A3 Gene-Disease associations (from GenCC):

• episodic ataxia type 6

  Inheritance: AD, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A3	NM_004172.5	c.319+5876G>T		intron_variant	Intron 3 of 9	ENST00000265113.9	NP_004163.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A3	ENST00000265113.9	c.319+5876G>T		intron_variant	Intron 3 of 9	1	NM_004172.5	ENSP00000265113.4

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77056 AN: 151910 Hom.: 20534 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.543

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.507 AC: 77092 AN: 152028 Hom.: 20550 Cov.: 32 AF XY: 0.510 AC XY: 37872 AN XY: 74278

African (AFR) AF: 0.336 AC: 13905 AN: 41428

American (AMR) AF: 0.546 AC: 8342 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1960 AN: 3472

East Asian (EAS) AF: 0.410 AC: 2120 AN: 5172

South Asian (SAS) AF: 0.582 AC: 2804 AN: 4816

European-Finnish (FIN) AF: 0.623 AC: 6573 AN: 10556

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39542 AN: 67980

Other (OTH) AF: 0.543 AC: 1148 AN: 2114

Alfa AF: 0.548 Hom.: 43307

Bravo AF: 0.494

Asia WGS AF: 0.531 AC: 1846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.0
DANN	Benign	0.82
PhyloP100		0.020
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1366632; hg19: chr5-36635565;