5-36618301-A-G

Variant names:

• chr5-36618301-A-G
• rs6451304
• NM_004172.5:c.181+9697A>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.181+9697A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,206 control chromosomes in the GnomAD database, including 3,032 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 0.16 (3032 hom., cov: 33)
• Consequence: SLC1A3 NM_004172.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475
• Publications: 3 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A3	NM_004172.5	MANE Select	c.181+9697A>G		intron	N/A	NP_004163.3
	SLC1A3	NM_001438458.1		c.181+9697A>G		intron	N/A	NP_001425387.1
	SLC1A3	NM_001438454.1		c.181+9697A>G		intron	N/A	NP_001425383.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A3	ENST00000265113.9	TSL:1 MANE Select	c.181+9697A>G		intron	N/A	ENSP00000265113.4	P43003-1
	SLC1A3	ENST00000381918.4	TSL:1	c.181+9697A>G		intron	N/A	ENSP00000371343.4	P43003-1
	SLC1A3	ENST00000680232.1		c.181+9697A>G		intron	N/A	ENSP00000506207.1	A0A7P0TAG7

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24138 AN: 152088 Hom.: 3028 Cov.: 33

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.0911

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0727

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.159 AC: 24169 AN: 152206 Hom.: 3032 Cov.: 33 AF XY: 0.158 AC XY: 11748 AN XY: 74428

African (AFR) AF: 0.342 AC: 14196 AN: 41482

American (AMR) AF: 0.0910 AC: 1391 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 550 AN: 3472

East Asian (EAS) AF: 0.201 AC: 1045 AN: 5188

South Asian (SAS) AF: 0.181 AC: 874 AN: 4822

European-Finnish (FIN) AF: 0.0651 AC: 690 AN: 10606

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0727 AC: 4947 AN: 68024

Other (OTH) AF: 0.128 AC: 270 AN: 2112

Alfa AF: 0.0961 Hom.: 1762

Bravo AF: 0.167

Asia WGS AF: 0.189 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.91
DANN	Benign	0.85
PhyloP100		-0.47
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: rs6451304; hg19: chr5-36618403;