5-36605258-C-T

Variant names:

• chr5-36605258-C-T
• rs2562582
• NM_001438455.1:c.-95-3071C>T

Variant summary

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

The NM_001438455.1(SLC1A3):​c.-95-3071C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 152,178 control chromosomes in the GnomAD database, including 56,684 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 0.86 (56684 hom., cov: 31)
• Consequence: SLC1A3 NM_001438455.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281
• Publications: 5 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

ENSG00000297790 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A3	NM_001438455.1	c.-95-3071C>T		intron_variant	Intron 1 of 9		NP_001425384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A3	ENST00000680318.1	c.-95-3071C>T		intron_variant	Intron 1 of 9			ENSP00000505057.1
ENSG00000297790	ENST00000750944.1	n.394+884G>A		intron_variant	Intron 2 of 2
ENSG00000297790	ENST00000750945.1	n.353+884G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130750 AN: 152060 Hom.: 56612 Cov.: 31

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.858

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

GnomAD4 genome AF: 0.860 AC: 130882 AN: 152178 Hom.: 56684 Cov.: 31 AF XY: 0.861 AC XY: 64040 AN XY: 74390

African (AFR) AF: 0.968 AC: 40217 AN: 41542

American (AMR) AF: 0.874 AC: 13372 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2565 AN: 3468

East Asian (EAS) AF: 0.886 AC: 4589 AN: 5180

South Asian (SAS) AF: 0.870 AC: 4195 AN: 4820

European-Finnish (FIN) AF: 0.792 AC: 8372 AN: 10568

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.806 AC: 54771 AN: 67990

Other (OTH) AF: 0.860 AC: 1816 AN: 2112

Alfa AF: 0.826 Hom.: 155588

Bravo AF: 0.870

Asia WGS AF: 0.905 AC: 3145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.93
DANN	Benign	0.44
PhyloP100		-0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2562582; hg19: chr5-36605360;