5-36648340-T-C

Variant names:

• chr5-36648340-T-C
• rs891189
• NM_004172.5:c.319+18753T>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.319+18753T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 152,062 control chromosomes in the GnomAD database, including 15,188 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 0.42 (15188 hom., cov: 32)
• Consequence: SLC1A3 NM_004172.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• Publications: 2 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 Gene-Disease associations (from GenCC):

• episodic ataxia type 6

  Inheritance: AD, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Laboratory for Molecular Medicine

ENSG00000274441 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A3	NM_004172.5	c.319+18753T>C		intron_variant	Intron 3 of 9	ENST00000265113.9	NP_004163.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A3	ENST00000265113.9	c.319+18753T>C		intron_variant	Intron 3 of 9	1	NM_004172.5	ENSP00000265113.4

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64123 AN: 151946 Hom.: 15187 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.422 AC: 64131 AN: 152062 Hom.: 15188 Cov.: 32 AF XY: 0.428 AC XY: 31835 AN XY: 74308

African (AFR) AF: 0.183 AC: 7592 AN: 41484

American (AMR) AF: 0.507 AC: 7739 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1711 AN: 3472

East Asian (EAS) AF: 0.537 AC: 2774 AN: 5166

South Asian (SAS) AF: 0.508 AC: 2446 AN: 4816

European-Finnish (FIN) AF: 0.559 AC: 5904 AN: 10562

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34346 AN: 67968

Other (OTH) AF: 0.467 AC: 986 AN: 2112

Alfa AF: 0.462 Hom.: 24281

Bravo AF: 0.410

Asia WGS AF: 0.497 AC: 1725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.64
PhyloP100		-0.26
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: rs891189; hg19: chr5-36648442;