5-36608922-T-C

Variant names:

• chr5-36608922-T-C
• rs13173144
• ENST00000512374.1:c.*301T>C

Variant summary

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

The NM_001166696.3(SLC1A3):​c.*301T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,060,234 control chromosomes in the GnomAD database, including 61,489 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 0.25 (5909 hom., cov: 33)
  • Exomes 𝑓: 0.34 (55580 hom.)
• Consequence: SLC1A3 NM_001166696.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 3 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: Unknown, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Laboratory for Molecular Medicine, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166696.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A3	NM_004172.5	MANE Select	c.181+318T>C		intron	N/A	NP_004163.3
	SLC1A3	NM_001166696.3		c.*301T>C		3_prime_UTR	Exon 2 of 2	NP_001160168.1	Q7Z5T0
	SLC1A3	NM_001438458.1		c.181+318T>C		intron	N/A	NP_001425387.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A3	ENST00000512374.1	TSL:1	c.*301T>C		3_prime_UTR	Exon 2 of 2	ENSP00000506048.1	Q7Z5T0
	SLC1A3	ENST00000265113.9	TSL:1 MANE Select	c.181+318T>C		intron	N/A	ENSP00000265113.4	P43003-1
	SLC1A3	ENST00000381918.4	TSL:1	c.181+318T>C		intron	N/A	ENSP00000371343.4	P43003-1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37992 AN: 152134 Hom.: 5912 Cov.: 33

Gnomad AFR AF: 0.0825

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.0944

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.258

GnomAD4 exome AF: 0.344 AC: 312293 AN: 907982 Hom.: 55580 Cov.: 28 AF XY: 0.344 AC XY: 145237 AN XY: 422810

African (AFR) AF: 0.0660 AC: 1207 AN: 18294

American (AMR) AF: 0.230 AC: 1149 AN: 4998

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 1720 AN: 8054

East Asian (EAS) AF: 0.0939 AC: 858 AN: 9140

South Asian (SAS) AF: 0.134 AC: 2770 AN: 20722

European-Finnish (FIN) AF: 0.369 AC: 1283 AN: 3476

Middle Eastern (MID) AF: 0.263 AC: 515 AN: 1958

European-Non Finnish (NFE) AF: 0.362 AC: 293126 AN: 809152

Other (OTH) AF: 0.300 AC: 9665 AN: 32188

GnomAD4 genome AF: 0.249 AC: 37984 AN: 152252 Hom.: 5909 Cov.: 33 AF XY: 0.246 AC XY: 18317 AN XY: 74430

African (AFR) AF: 0.0824 AC: 3424 AN: 41558

American (AMR) AF: 0.252 AC: 3852 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 710 AN: 3472

East Asian (EAS) AF: 0.0946 AC: 491 AN: 5188

South Asian (SAS) AF: 0.134 AC: 645 AN: 4828

European-Finnish (FIN) AF: 0.351 AC: 3714 AN: 10584

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.356 AC: 24233 AN: 67996

Other (OTH) AF: 0.254 AC: 538 AN: 2114

Alfa AF: 0.283 Hom.: 1579

Bravo AF: 0.234

Asia WGS AF: 0.106 AC: 368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.6
DANN	Benign	0.62
PhyloP100		-2.0
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: rs13173144; hg19: chr5-36609024;