5-36678173-T-C

Variant names:

• chr5-36678173-T-C
• rs2301066
• NM_004172.5:c.860+989T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004172.5(SLC1A3):​c.860+989T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 151,858 control chromosomes in the GnomAD database, including 19,633 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 0.50 (19633 hom., cov: 32)
• Consequence: SLC1A3 NM_004172.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A3	NM_004172.5	c.860+989T>C		intron_variant	Intron 6 of 9	ENST00000265113.9	NP_004163.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A3	ENST00000265113.9	c.860+989T>C		intron_variant	Intron 6 of 9	1	NM_004172.5	ENSP00000265113.4

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76365 AN: 151738 Hom.: 19624 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.619

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.503 AC: 76406 AN: 151858 Hom.: 19633 Cov.: 32 AF XY: 0.506 AC XY: 37586 AN XY: 74222

African (AFR) AF: 0.405 AC: 16769 AN: 41428

American (AMR) AF: 0.543 AC: 8267 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1724 AN: 3398

East Asian (EAS) AF: 0.533 AC: 2754 AN: 5170

South Asian (SAS) AF: 0.413 AC: 1989 AN: 4820

European-Finnish (FIN) AF: 0.635 AC: 6726 AN: 10590

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.536 AC: 36406 AN: 67904

Other (OTH) AF: 0.525 AC: 1108 AN: 2110

Alfa AF: 0.525 Hom.: 75317

Bravo AF: 0.497

Asia WGS AF: 0.478 AC: 1663 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	7.3
DANN	Benign	0.71
PhyloP100		-0.19
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: rs2301066; hg19: chr5-36678275;