chr5-36600817-T-G

Variant names:

• chr5-36600817-T-G
• rs4869675
• NM_001438455.1:c.-96+4139T>G

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+4139T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,026 control chromosomes in the GnomAD database, including 8,240 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 0.33 (8240 hom., cov: 32)
• Consequence: SLC1A3 NM_001438455.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250
• Publications: 6 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: Unknown, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Laboratory for Molecular Medicine, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia

ENSG00000297790 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.429 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A3	NM_001438455.1		c.-96+4139T>G		intron	N/A	NP_001425384.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A3	ENST00000680318.1		c.-96+4139T>G		intron	N/A	ENSP00000505057.1	P43003-1
	SLC1A3	ENST00000936087.1		c.-96+4139T>G		intron	N/A	ENSP00000606146.1
	SLC1A3	ENST00000936088.1		c.-96+4139T>G		intron	N/A	ENSP00000606147.1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49587 AN: 151908 Hom.: 8231 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.326 AC: 49615 AN: 152026 Hom.: 8240 Cov.: 32 AF XY: 0.330 AC XY: 24486 AN XY: 74300

African (AFR) AF: 0.310 AC: 12873 AN: 41472

American (AMR) AF: 0.410 AC: 6269 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1142 AN: 3472

East Asian (EAS) AF: 0.284 AC: 1469 AN: 5174

South Asian (SAS) AF: 0.445 AC: 2141 AN: 4812

European-Finnish (FIN) AF: 0.318 AC: 3350 AN: 10544

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21213 AN: 67956

Other (OTH) AF: 0.355 AC: 749 AN: 2108

Alfa AF: 0.316 Hom.: 11457

Bravo AF: 0.330

Asia WGS AF: 0.382 AC: 1326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.2
DANN	Benign	0.67
PhyloP100		-0.025

Splicing

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

Other links and lift over

dbSNP: rs4869675; hg19: chr5-36600919;