chr5-36644198-G-A

Variant names:

• chr5-36644198-G-A
• rs1645660
• NM_004172.5:c.319+14611G>A

Variant summary

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

The NM_004172.5(SLC1A3):​c.319+14611G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,282 control chromosomes in the GnomAD database, including 10,294 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 0.35 (10294 hom., cov: 29)
• Consequence: SLC1A3 NM_004172.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.432 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.319+14611G>A		intron	N/A	NP_004163.3
	SLC1A3	NM_001438458.1		c.319+14611G>A		intron	N/A	NP_001425387.1
	SLC1A3	NM_001438454.1		c.319+14611G>A		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+14611G>A		intron	N/A	ENSP00000265113.4
	SLC1A3	ENST00000381918.4	TSL:1	c.319+14611G>A		intron	N/A	ENSP00000371343.4
	SLC1A3	ENST00000680232.1		c.319+14611G>A		intron	N/A	ENSP00000506207.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52643 AN: 151164 Hom.: 10284 Cov.: 29

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.348 AC: 52665 AN: 151282 Hom.: 10294 Cov.: 29 AF XY: 0.354 AC XY: 26118 AN XY: 73798

African (AFR) AF: 0.153 AC: 6292 AN: 41234

American (AMR) AF: 0.398 AC: 6050 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1327 AN: 3462

East Asian (EAS) AF: 0.382 AC: 1963 AN: 5138

South Asian (SAS) AF: 0.447 AC: 2135 AN: 4772

European-Finnish (FIN) AF: 0.469 AC: 4854 AN: 10344

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28690 AN: 67852

Other (OTH) AF: 0.397 AC: 831 AN: 2092

Alfa AF: 0.409 Hom.: 21891

Bravo AF: 0.337

Asia WGS AF: 0.401 AC: 1392 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.5
DANN	Benign	0.80
PhyloP100		0.17
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: rs1645660; hg19: chr5-36644300;