chr5-36609059-A-T

Position:

• chr5-36609059-A-T

Variant summary

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

The NM_001166696.3(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 NM_001166696.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A3	NM_004172.5	c.181+455A>T		intron_variant		ENST00000265113.9	NP_004163.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A3	ENST00000265113.9	c.181+455A>T		intron_variant		1	NM_004172.5	ENSP00000265113.4

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

Gnomad4 AFR exome AF: 0.283

Gnomad4 AMR exome AF: 0.469

Gnomad4 ASJ exome AF: 0.347

Gnomad4 EAS exome AF: 0.327

Gnomad4 SAS exome AF: 0.476

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.313

Gnomad4 OTH exome AF: 0.337

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

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.375

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.5
DANN	Benign	0.44

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: rs4869676; hg19: chr5-36609161;