rs3776572

Variant names:

• chr5-36645930-C-G
• rs3776572
• NM_004172.5:c.319+16343C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-36645930-C-G
• chr5-36645930-C-T

Variant summary

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

The NM_001438458.1(SLC1A3):​c.319+16343C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,082 control chromosomes in the GnomAD database, including 27,949 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 0.59 (27949 hom., cov: 32)
• Consequence: SLC1A3 NM_001438458.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001438458.1. 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.319+16343C>G		intron	N/A	NP_004163.3
	SLC1A3	NM_001438458.1		c.319+16343C>G		intron	N/A	NP_001425387.1
	SLC1A3	NM_001438454.1		c.319+16343C>G		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.319+16343C>G		intron	N/A	ENSP00000265113.4
	SLC1A3	ENST00000381918.4	TSL:1	c.319+16343C>G		intron	N/A	ENSP00000371343.4
	SLC1A3	ENST00000680232.1		c.319+16343C>G		intron	N/A	ENSP00000506207.1

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89582 AN: 151964 Hom.: 27954 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.589 AC: 89591 AN: 152082 Hom.: 27949 Cov.: 32 AF XY: 0.593 AC XY: 44093 AN XY: 74334

African (AFR) AF: 0.363 AC: 15053 AN: 41446

American (AMR) AF: 0.644 AC: 9851 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2134 AN: 3470

East Asian (EAS) AF: 0.595 AC: 3075 AN: 5168

South Asian (SAS) AF: 0.624 AC: 3015 AN: 4830

European-Finnish (FIN) AF: 0.731 AC: 7745 AN: 10588

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.686 AC: 46641 AN: 67978

Other (OTH) AF: 0.615 AC: 1296 AN: 2106

Alfa AF: 0.640 Hom.: 4008

Bravo AF: 0.575

Asia WGS AF: 0.564 AC: 1962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.80
PhyloP100		-0.0020
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: rs3776572; hg19: chr5-36646032;