NM_004172.5:c.181+8108T>C

Variant names:

• chr5-36616712-T-C
• rs10512660
• NM_004172.5:c.181+8108T>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+8108T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,200 control chromosomes in the GnomAD database, including 1,382 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 (1382 hom., cov: 32)
• Consequence: SLC1A3 NM_004172.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.554
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A3	NM_004172.5	c.181+8108T>C		intron_variant	Intron 2 of 9	ENST00000265113.9	NP_004163.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A3	ENST00000265113.9	c.181+8108T>C		intron_variant	Intron 2 of 9	1	NM_004172.5	ENSP00000265113.4

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16777 AN: 152082 Hom.: 1371 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0675

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0578

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0537

Gnomad OTH AF: 0.0905

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

GnomAD4 genome AF: 0.110 AC: 16813 AN: 152200 Hom.: 1382 Cov.: 32 AF XY: 0.112 AC XY: 8335 AN XY: 74408

African (AFR) AF: 0.214 AC: 8875 AN: 41516

American (AMR) AF: 0.0672 AC: 1027 AN: 15292

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

East Asian (EAS) AF: 0.291 AC: 1501 AN: 5166

South Asian (SAS) AF: 0.106 AC: 512 AN: 4818

European-Finnish (FIN) AF: 0.0578 AC: 613 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0537 AC: 3654 AN: 68012

Other (OTH) AF: 0.0910 AC: 192 AN: 2110

Alfa AF: 0.0907 Hom.: 132

Bravo AF: 0.116

Asia WGS AF: 0.177 AC: 612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.3
DANN	Benign	0.59
PhyloP100		0.55
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: rs10512660; hg19: chr5-36616814;