rs9292638

Positions:

• chr5-36617233-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A3	NM_004172.5	c.181+8629G>C		intron_variant		ENST00000265113.9	NP_004163.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A3	ENST00000265113.9	c.181+8629G>C		intron_variant		1	NM_004172.5	ENSP00000265113	P1

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

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.0666

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0573

Gnomad4 NFE AF: 0.0537

Gnomad4 OTH AF: 0.0882

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.58
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs9292638; hg19: chr5-36617335;