5-36617233-G-C

Variant names:

• chr5-36617233-G-C
• rs9292638
• NM_004172.5:c.181+8629G>C

Variant summary

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

The NM_004172.5(SLC1A3):​c.181+8629G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,090 control chromosomes in the GnomAD database, including 1,207 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 0.11 (1207 hom., cov: 32)
• Consequence: SLC1A3 NM_004172.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.460
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004172.5. 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_004172.5	MANE Select	c.181+8629G>C		intron	N/A	NP_004163.3
	SLC1A3	NM_001438458.1		c.181+8629G>C		intron	N/A	NP_001425387.1
	SLC1A3	NM_001438454.1		c.181+8629G>C		intron	N/A	NP_001425383.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A3	ENST00000265113.9	TSL:1 MANE Select	c.181+8629G>C		intron	N/A	ENSP00000265113.4
	SLC1A3	ENST00000381918.4	TSL:1	c.181+8629G>C		intron	N/A	ENSP00000371343.4
	SLC1A3	ENST00000680232.1		c.181+8629G>C		intron	N/A	ENSP00000506207.1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15977 AN: 151972 Hom.: 1199 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.0670

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0573

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0537

Gnomad OTH AF: 0.0877

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

GnomAD4 genome AF: 0.105 AC: 16003 AN: 152090 Hom.: 1207 Cov.: 32 AF XY: 0.107 AC XY: 7942 AN XY: 74352

African (AFR) AF: 0.195 AC: 8106 AN: 41488

American (AMR) AF: 0.0666 AC: 1018 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 373 AN: 3470

East Asian (EAS) AF: 0.290 AC: 1493 AN: 5154

South Asian (SAS) AF: 0.105 AC: 506 AN: 4818

European-Finnish (FIN) AF: 0.0573 AC: 606 AN: 10576

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0537 AC: 3650 AN: 67994

Other (OTH) AF: 0.0882 AC: 186 AN: 2108

Alfa AF: 0.0827 Hom.: 100

Bravo AF: 0.111

Asia WGS AF: 0.174 AC: 604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.58
DANN	Benign	0.36
PhyloP100		-0.46
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: rs9292638; hg19: chr5-36617335;