5-36670903-T-C

Position:

• chr5-36670903-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004172.5(SLC1A3):​c.320-126T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.049 in 835,948 control chromosomes in the GnomAD database, including 1,293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (184 hom., cov: 32)
  • Exomes 𝑓: 0.051 (1109 hom.)
• Consequence: SLC1A3 NM_004172.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.125

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-36670903-T-C is Benign according to our data. Variant chr5-36670903-T-C is described in ClinVar as [Benign]. Clinvar id is 1293137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A3	NM_004172.5	c.320-126T>C		intron_variant		ENST00000265113.9	NP_004163.3
SLC1A3-AS1	XR_007058736.1	n.76-2192A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A3	ENST00000265113.9	c.320-126T>C		intron_variant		1	NM_004172.5	ENSP00000265113	P1
SLC1A3-AS1	ENST00000510740.1	n.61-2192A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0400 AC: 6088 AN: 152140 Hom.: 184 Cov.: 32

Gnomad AFR AF: 0.00927

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0380

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0375

Gnomad FIN AF: 0.0372

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0586

Gnomad OTH AF: 0.0416

GnomAD4 exome AF: 0.0510 AC: 34873 AN: 683690 Hom.: 1109 Cov.: 9 AF XY: 0.0512 AC XY: 18473 AN XY: 360514

Gnomad4 AFR exome AF: 0.0100

Gnomad4 AMR exome AF: 0.0297

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.0000615

Gnomad4 SAS exome AF: 0.0426

Gnomad4 FIN exome AF: 0.0469

Gnomad4 NFE exome AF: 0.0568

Gnomad4 OTH exome AF: 0.0530

GnomAD4 genome AF: 0.0400 AC: 6083 AN: 152258 Hom.: 184 Cov.: 32 AF XY: 0.0390 AC XY: 2905 AN XY: 74460

Gnomad4 AFR AF: 0.00924

Gnomad4 AMR AF: 0.0379

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0376

Gnomad4 FIN AF: 0.0372

Gnomad4 NFE AF: 0.0586

Gnomad4 OTH AF: 0.0412

Alfa AF: 0.0500 Hom.: 25

Bravo AF: 0.0384

Asia WGS AF: 0.0160 AC: 54 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.70

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: rs962686; hg19: chr5-36671005;