chr5-36624000-G-C

Variant names:

• chr5-36624000-G-C
• rs10941306
• NM_004172.5:c.182-5450G>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.182-5450G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,048 control chromosomes in the GnomAD database, including 32,274 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 0.65 (32274 hom., cov: 32)
• Consequence: SLC1A3 NM_004172.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574
• Publications: 1 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004172.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A3	NM_004172.5	MANE Select	c.182-5450G>C		intron	N/A	NP_004163.3
	SLC1A3	NM_001438458.1		c.182-5450G>C		intron	N/A	NP_001425387.1
	SLC1A3	NM_001438454.1		c.182-5450G>C		intron	N/A	NP_001425383.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A3	ENST00000265113.9	TSL:1 MANE Select	c.182-5450G>C		intron	N/A	ENSP00000265113.4
	SLC1A3	ENST00000381918.4	TSL:1	c.182-5450G>C		intron	N/A	ENSP00000371343.4
	SLC1A3	ENST00000680232.1		c.182-5450G>C		intron	N/A	ENSP00000506207.1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98575 AN: 151930 Hom.: 32245 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.649 AC: 98660 AN: 152048 Hom.: 32274 Cov.: 32 AF XY: 0.654 AC XY: 48626 AN XY: 74300

African (AFR) AF: 0.576 AC: 23862 AN: 41454

American (AMR) AF: 0.715 AC: 10935 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2421 AN: 3470

East Asian (EAS) AF: 0.685 AC: 3546 AN: 5178

South Asian (SAS) AF: 0.724 AC: 3494 AN: 4824

European-Finnish (FIN) AF: 0.716 AC: 7559 AN: 10558

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.657 AC: 44635 AN: 67974

Other (OTH) AF: 0.684 AC: 1438 AN: 2102

Alfa AF: 0.638 Hom.: 3699

Bravo AF: 0.647

Asia WGS AF: 0.730 AC: 2534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.9
DANN	Benign	0.53
PhyloP100		-0.57
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: rs10941306; hg19: chr5-36624102;