rs2269272

Variant names:

• chr5-36687754-C-T
• rs2269272
• NM_004172.5:c.*1485C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0790
• Publications: 18 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-AS1 (HGNC:56374): (SLC1A3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 353354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
SLC1A3	NM_004172.5	c.*1485C>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000265113.9	NP_004163.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A3	ENST00000265113.9	c.*1485C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_004172.5	ENSP00000265113.4

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.296 AC: 125 AN: 422

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

African (AFR) AF: 0.0828 AC: 3432 AN: 41458

American (AMR) AF: 0.295 AC: 4500 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 678 AN: 3470

East Asian (EAS) AF: 0.268 AC: 1386 AN: 5178

South Asian (SAS) AF: 0.190 AC: 911 AN: 4802

European-Finnish (FIN) AF: 0.295 AC: 3108 AN: 10552

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13096 AN: 67974

Other (OTH) AF: 0.205 AC: 433 AN: 2110

Alfa AF: 0.191 Hom.: 8453

Bravo AF: 0.183

Asia WGS AF: 0.207 AC: 717 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Episodic ataxia type 6 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		-0.079
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: rs2269272; hg19: chr5-36687856; COSMIC: COSV54320453; COSMIC: COSV54320453;