5-36608922-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000512374.1(SLC1A3):c.*301T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,060,234 control chromosomes in the GnomAD database, including 61,489 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 0.25 (5909 hom., cov: 33)
  • Exomes 𝑓: 0.34 (55580 hom.)
• Consequence: SLC1A3 ENST00000512374.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A3	NM_004172.5	c.181+318T>C		intron_variant		ENST00000265113.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A3	ENST00000265113.9	c.181+318T>C		intron_variant		1	NM_004172.5	P1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37992 AN: 152134 Hom.: 5912 Cov.: 33

Gnomad AFR AF: 0.0825

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.0944

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.258

GnomAD4 exome AF: 0.344 AC: 312293 AN: 907982 Hom.: 55580 Cov.: 28 AF XY: 0.344 AC XY: 145237 AN XY: 422810

Gnomad4 AFR exome AF: 0.0660

Gnomad4 AMR exome AF: 0.230

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.0939

Gnomad4 SAS exome AF: 0.134

Gnomad4 FIN exome AF: 0.369

Gnomad4 NFE exome AF: 0.362

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.249 AC: 37984 AN: 152252 Hom.: 5909 Cov.: 33 AF XY: 0.246 AC XY: 18317 AN XY: 74430

Gnomad4 AFR AF: 0.0824

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.0946

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.254

Alfa AF: 0.287 Hom.: 1570

Bravo AF: 0.234

Asia WGS AF: 0.106 AC: 368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	2.6
Dann	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs13173144; hg19: chr5-36609024;