5-36661842-A-G

Variant names:

• chr5-36661842-A-G
• rs3776581
• NM_004172.5:c.320-9187A>G

Variant summary

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

The NM_004172.5(SLC1A3):​c.320-9187A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,132 control chromosomes in the GnomAD database, including 30,996 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 0.62 (30996 hom., cov: 33)
• Consequence: SLC1A3 NM_004172.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 5 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=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.717 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.320-9187A>G		intron	N/A	NP_004163.3
	SLC1A3	NM_001438458.1		c.320-9187A>G		intron	N/A	NP_001425387.1
	SLC1A3	NM_001438454.1		c.320-9187A>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.320-9187A>G		intron	N/A	ENSP00000265113.4
	SLC1A3	ENST00000381918.4	TSL:1	c.320-9187A>G		intron	N/A	ENSP00000371343.4
	SLC1A3	ENST00000680232.1		c.320-9187A>G		intron	N/A	ENSP00000506207.1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93575 AN: 152014 Hom.: 30995 Cov.: 33

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.615 AC: 93600 AN: 152132 Hom.: 30996 Cov.: 33 AF XY: 0.618 AC XY: 45926 AN XY: 74368

African (AFR) AF: 0.347 AC: 14382 AN: 41466

American (AMR) AF: 0.709 AC: 10840 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2129 AN: 3470

East Asian (EAS) AF: 0.719 AC: 3716 AN: 5170

South Asian (SAS) AF: 0.710 AC: 3423 AN: 4820

European-Finnish (FIN) AF: 0.742 AC: 7856 AN: 10590

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.723 AC: 49156 AN: 68006

Other (OTH) AF: 0.624 AC: 1319 AN: 2114

Alfa AF: 0.692 Hom.: 41000

Bravo AF: 0.604

Asia WGS AF: 0.660 AC: 2292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Benign	0.79
PhyloP100		1.3
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: rs3776581; hg19: chr5-36661944;