rs1645660

chr5-36644198-G-A

Variant summary

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

The NM_004172.5(SLC1A3):c.319+14611G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,282 control chromosomes in the GnomAD database, including 10,294 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 0.35 (10294 hom., cov: 29)
• Consequence: SLC1A3 NM_004172.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A3	NM_004172.5	c.319+14611G>A		intron_variant		ENST00000265113.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A3	ENST00000265113.9	c.319+14611G>A		intron_variant		1	NM_004172.5	P1
	ENST00000618632.1	n.33+5117C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52643 AN: 151164 Hom.: 10284 Cov.: 29

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.398

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.348 AC: 52665 AN: 151282 Hom.: 10294 Cov.: 29 AF XY: 0.354 AC XY: 26118 AN XY: 73798

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.397

Alfa AF: 0.418 Hom.: 17738

Bravo AF: 0.337

Asia WGS AF: 0.401 AC: 1392 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	4.5
Dann	Benign	0.80

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: rs1645660; hg19: chr5-36644300;