5-36646813-A-G

Variant names:

• chr5-36646813-A-G
• rs1428967
• NM_004172.5:c.319+17226A>G

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+17226A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,196 control chromosomes in the GnomAD database, including 2,690 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 0.17 (2690 hom., cov: 32)
• Consequence: SLC1A3 NM_004172.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366
• Publications: 4 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

ENSG00000274441 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A3	NM_004172.5	c.319+17226A>G		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+17226A>G		intron_variant	Intron 3 of 9	1	NM_004172.5	ENSP00000265113.4

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26257 AN: 152078 Hom.: 2689 Cov.: 32

Gnomad AFR AF: 0.0631

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.173 AC: 26278 AN: 152196 Hom.: 2690 Cov.: 32 AF XY: 0.169 AC XY: 12611 AN XY: 74418

African (AFR) AF: 0.0635 AC: 2636 AN: 41544

American (AMR) AF: 0.191 AC: 2925 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 811 AN: 3472

East Asian (EAS) AF: 0.123 AC: 637 AN: 5178

South Asian (SAS) AF: 0.200 AC: 963 AN: 4826

European-Finnish (FIN) AF: 0.179 AC: 1896 AN: 10584

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15812 AN: 67994

Other (OTH) AF: 0.169 AC: 357 AN: 2114

Alfa AF: 0.197 Hom.: 1166

Bravo AF: 0.169

Asia WGS AF: 0.165 AC: 576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.5
DANN	Benign	0.60
PhyloP100		0.37
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: rs1428967; hg19: chr5-36646915;