rs2269272

chr5-36687754-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004172.5(SLC1A3):c.*1485C>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 0.183 in 152,438 control chromosomes in the GnomAD database, including 3,036 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (3018 hom., cov: 32)
  • Exomes 𝑓: 0.30 (18 hom.)
• Consequence: SLC1A3 NM_004172.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0790

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-AS1 (HGNC:56374): (SLC1A3 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-36687754-C-T is Benign according to our data. Variant chr5-36687754-C-T is described in ClinVar as [Benign]. Clinvar id is 353354.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A3	NM_004172.5	c.*1485C>T		3_prime_UTR_variant	10/10	ENST00000265113.9
SLC1A3-AS1	XR_007058736.1	n.76-19043G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A3	ENST00000265113.9	c.*1485C>T		3_prime_UTR_variant	10/10	1	NM_004172.5	P1
SLC1A3-AS1	ENST00000510740.1	n.61-19043G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27746 AN: 151894 Hom.: 3017 Cov.: 32

Gnomad AFR AF: 0.0828

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.206

GnomAD4 exome AF: 0.297 AC: 127 AN: 428 Hom.: 18 Cov.: 0 AF XY: 0.305 AC XY: 78 AN XY: 256

Gnomad4 FIN exome AF: 0.296

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.183 AC: 27759 AN: 152010 Hom.: 3018 Cov.: 32 AF XY: 0.188 AC XY: 14001 AN XY: 74282

Gnomad4 AFR AF: 0.0828

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.205

Alfa AF: 0.194 Hom.: 5286

Bravo AF: 0.183

Asia WGS AF: 0.207 AC: 717 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Episodic ataxia type 6 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	6.7
Dann	Benign	0.58

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: rs2269272; hg19: chr5-36687856; COSMIC: COSV54320453; COSMIC: COSV54320453;