ENST00000512374.1:c.*438A>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000512374.1(SLC1A3):​c.*438A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 989,946 control chromosomes in the GnomAD database, including 51,175 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 0.33 (8682 hom., cov: 32)
  • Exomes 𝑓: 0.32 (42493 hom.)
• Consequence: SLC1A3 ENST00000512374.1 3_prime_UTR
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000512374.1. 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+455A>T		intron	N/A	NP_004163.3
	SLC1A3	NM_001166696.3		c.*438A>T		3_prime_UTR	Exon 2 of 2	NP_001160168.1
	SLC1A3	NM_001438458.1		c.181+455A>T		intron	N/A	NP_001425387.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50491 AN: 151998 Hom.: 8666 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.373

GnomAD4 exome AF: 0.317 AC: 265729 AN: 837830 Hom.: 42493 Cov.: 27 AF XY: 0.317 AC XY: 122749 AN XY: 387354

African (AFR) AF: 0.283 AC: 4479 AN: 15816

American (AMR) AF: 0.469 AC: 852 AN: 1816

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1806 AN: 5210

East Asian (EAS) AF: 0.327 AC: 1269 AN: 3880

South Asian (SAS) AF: 0.476 AC: 8050 AN: 16904

European-Finnish (FIN) AF: 0.265 AC: 108 AN: 408

Middle Eastern (MID) AF: 0.368 AC: 597 AN: 1624

European-Non Finnish (NFE) AF: 0.313 AC: 239301 AN: 764676

Other (OTH) AF: 0.337 AC: 9267 AN: 27496

GnomAD4 genome AF: 0.332 AC: 50532 AN: 152116 Hom.: 8682 Cov.: 32 AF XY: 0.336 AC XY: 24988 AN XY: 74342

African (AFR) AF: 0.290 AC: 12039 AN: 41478

American (AMR) AF: 0.456 AC: 6978 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1266 AN: 3472

East Asian (EAS) AF: 0.321 AC: 1659 AN: 5172

South Asian (SAS) AF: 0.491 AC: 2369 AN: 4826

European-Finnish (FIN) AF: 0.317 AC: 3350 AN: 10578

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21669 AN: 67984

Other (OTH) AF: 0.375 AC: 791 AN: 2108

Alfa AF: 0.315 Hom.: 1063

Bravo AF: 0.338

Asia WGS AF: 0.466 AC: 1618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.5
DANN	Benign	0.44
PhyloP100		1.4
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: rs4869676; hg19: chr5-36609161;