rs4869676

Variant names:

• chr5-36609059-A-G
• rs4869676
• ENST00000512374.1:c.*438A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-36609059-A-G
• chr5-36609059-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000265113.9(SLC1A3):​c.181+455A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000119 in 838,404 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: SLC1A3 ENST00000265113.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 6 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000265113.9. 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+455A>G		intron	N/A	NP_004163.3
	SLC1A3	NM_001166696.3		c.*438A>G		3_prime_UTR	Exon 2 of 2	NP_001160168.1
	SLC1A3	NM_001438458.1		c.181+455A>G		intron	N/A	NP_001425387.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A3	ENST00000512374.1	TSL:1	c.*438A>G		3_prime_UTR	Exon 2 of 2	ENSP00000506048.1
	SLC1A3	ENST00000265113.9	TSL:1 MANE Select	c.181+455A>G		intron	N/A	ENSP00000265113.4
	SLC1A3	ENST00000381918.4	TSL:1	c.181+455A>G		intron	N/A	ENSP00000371343.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000119 AC: 1 AN: 838404 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 387590

African (AFR) AF: 0.00 AC: 0 AN: 15818

American (AMR) AF: 0.00 AC: 0 AN: 1818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5214

East Asian (EAS) AF: 0.00 AC: 0 AN: 3890

South Asian (SAS) AF: 0.00 AC: 0 AN: 16914

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1626

European-Non Finnish (NFE) AF: 0.00000131 AC: 1 AN: 765204

Other (OTH) AF: 0.00 AC: 0 AN: 27512

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1063

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	0.30
PhyloP100		1.4

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: rs4869676; hg19: chr5-36609161;