5-36636737-A-T

Variant names:

• chr5-36636737-A-T
• rs7734056
• NM_004172.5:c.319+7150A>T

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+7150A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 151,552 control chromosomes in the GnomAD database, including 1,410 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 0.12 (1410 hom., cov: 29)
• Consequence: SLC1A3 NM_004172.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• 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: Unknown, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Laboratory for Molecular Medicine, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia

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 = 0.165 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.319+7150A>T		intron	N/A	NP_004163.3
	SLC1A3	NM_001438458.1		c.319+7150A>T		intron	N/A	NP_001425387.1
	SLC1A3	NM_001438454.1		c.319+7150A>T		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.319+7150A>T		intron	N/A	ENSP00000265113.4	P43003-1
	SLC1A3	ENST00000381918.4	TSL:1	c.319+7150A>T		intron	N/A	ENSP00000371343.4	P43003-1
	SLC1A3	ENST00000680232.1		c.319+7150A>T		intron	N/A	ENSP00000506207.1	A0A7P0TAG7

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18704 AN: 151438 Hom.: 1408 Cov.: 29

Gnomad AFR AF: 0.0311

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.0708

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.123 AC: 18710 AN: 151552 Hom.: 1410 Cov.: 29 AF XY: 0.123 AC XY: 9099 AN XY: 74028

African (AFR) AF: 0.0310 AC: 1283 AN: 41352

American (AMR) AF: 0.151 AC: 2295 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 643 AN: 3468

East Asian (EAS) AF: 0.0708 AC: 363 AN: 5130

South Asian (SAS) AF: 0.146 AC: 703 AN: 4802

European-Finnish (FIN) AF: 0.158 AC: 1646 AN: 10430

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11349 AN: 67828

Other (OTH) AF: 0.128 AC: 270 AN: 2108

Alfa AF: 0.135 Hom.: 201

Bravo AF: 0.118

Asia WGS AF: 0.125 AC: 437 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.1
DANN	Benign	0.81
PhyloP100		-0.057
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: rs7734056; hg19: chr5-36636839;