5-36601753-T-C

Variant names:

• chr5-36601753-T-C
• rs2731877
• NM_001438455.1:c.-96+5075T>C

Variant summary

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

The NM_001438455.1(SLC1A3):​c.-96+5075T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 150,704 control chromosomes in the GnomAD database, including 21,265 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 0.52 (21265 hom., cov: 26)
• Consequence: SLC1A3 NM_001438455.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001438455.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A3	NM_001438455.1		c.-96+5075T>C		intron	N/A	NP_001425384.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A3	ENST00000680318.1		c.-96+5075T>C		intron	N/A	ENSP00000505057.1
	ENSG00000297790	ENST00000750944.1		n.394+4389A>G		intron	N/A
	ENSG00000297790	ENST00000750945.1		n.353+4389A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.523 AC: 78826 AN: 150594 Hom.: 21227 Cov.: 26

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.524 AC: 78906 AN: 150704 Hom.: 21265 Cov.: 26 AF XY: 0.519 AC XY: 38174 AN XY: 73510

African (AFR) AF: 0.655 AC: 26786 AN: 40896

American (AMR) AF: 0.415 AC: 6303 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1379 AN: 3464

East Asian (EAS) AF: 0.541 AC: 2761 AN: 5104

South Asian (SAS) AF: 0.387 AC: 1830 AN: 4734

European-Finnish (FIN) AF: 0.468 AC: 4827 AN: 10306

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.494 AC: 33432 AN: 67718

Other (OTH) AF: 0.482 AC: 1011 AN: 2098

Alfa AF: 0.489 Hom.: 20795

Bravo AF: 0.528

Asia WGS AF: 0.429 AC: 1493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.51
PhyloP100		-0.25

Splicing

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

Other links and lift over

dbSNP: rs2731877; hg19: chr5-36601855; COSMIC: COSV54316583;