NM_004172.5:c.181+7829A>G

Variant names:

• chr5-36616433-A-G
• rs1366638
• NM_004172.5:c.181+7829A>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.181+7829A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 152,160 control chromosomes in the GnomAD database, including 50,632 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 0.81 (50632 hom., cov: 32)
• Consequence: SLC1A3 NM_004172.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.511
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 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.181+7829A>G		intron	N/A	NP_004163.3
	SLC1A3	NM_001438458.1		c.181+7829A>G		intron	N/A	NP_001425387.1
	SLC1A3	NM_001438454.1		c.181+7829A>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.181+7829A>G		intron	N/A	ENSP00000265113.4
	SLC1A3	ENST00000381918.4	TSL:1	c.181+7829A>G		intron	N/A	ENSP00000371343.4
	SLC1A3	ENST00000680232.1		c.181+7829A>G		intron	N/A	ENSP00000506207.1

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123297 AN: 152042 Hom.: 50574 Cov.: 32

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.896

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.811 AC: 123413 AN: 152160 Hom.: 50632 Cov.: 32 AF XY: 0.815 AC XY: 60651 AN XY: 74386

African (AFR) AF: 0.930 AC: 38634 AN: 41536

American (AMR) AF: 0.808 AC: 12353 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.847 AC: 2942 AN: 3472

East Asian (EAS) AF: 0.887 AC: 4593 AN: 5180

South Asian (SAS) AF: 0.895 AC: 4299 AN: 4806

European-Finnish (FIN) AF: 0.780 AC: 8258 AN: 10582

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.731 AC: 49674 AN: 67984

Other (OTH) AF: 0.813 AC: 1718 AN: 2114

Alfa AF: 0.756 Hom.: 68940

Bravo AF: 0.818

Asia WGS AF: 0.917 AC: 3187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.6
DANN	Benign	0.50
PhyloP100		0.51
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: rs1366638; hg19: chr5-36616535; COSMIC: COSV54320567; COSMIC: COSV54320567;