rs143791614

Variant names:

• chr5-36608438-T-C
• rs143791614
• NM_004172.5:c.15T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-36608438-T-C
• chr5-36608438-T-G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_004172.5(SLC1A3):​c.15T>C​(p.Asn5Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000729 in 1,613,780 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00062 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00074 (2 hom.)
• Consequence: SLC1A3 NM_004172.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.0520
• Publications: 0 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), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 5-36608438-T-C is Benign according to our data. Variant chr5-36608438-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 353306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.052 with no splicing effect.
• BS2: High AC in GnomAd4 at 95 Unknown,AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A3	NM_004172.5	MANE Select	c.15T>C	p.Asn5Asn	synonymous	Exon 2 of 10	NP_004163.3
	SLC1A3	NM_001438458.1		c.15T>C	p.Asn5Asn	synonymous	Exon 2 of 11	NP_001425387.1
	SLC1A3	NM_001438454.1		c.15T>C	p.Asn5Asn	synonymous	Exon 3 of 11	NP_001425383.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A3	ENST00000265113.9	TSL:1 MANE Select	c.15T>C	p.Asn5Asn	synonymous	Exon 2 of 10	ENSP00000265113.4	P43003-1
	SLC1A3	ENST00000381918.4	TSL:1	c.15T>C	p.Asn5Asn	synonymous	Exon 2 of 10	ENSP00000371343.4	P43003-1
	SLC1A3	ENST00000512374.1	TSL:1	c.15T>C	p.Asn5Asn	synonymous	Exon 2 of 2	ENSP00000506048.1	Q7Z5T0

Frequencies

GnomAD3 genomes AF: 0.000625 AC: 95 AN: 151964 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.000662

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00106

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000573 AC: 144 AN: 251244 AF XY: 0.000685

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00116

Gnomad NFE exome AF: 0.000748

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000740 AC: 1081 AN: 1461698 Hom.: 2 Cov.: 31 AF XY: 0.000754 AC XY: 548 AN XY: 727144

African (AFR) AF: 0.0000598 AC: 2 AN: 33462

American (AMR) AF: 0.0000895 AC: 4 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000765 AC: 66 AN: 86258

European-Finnish (FIN) AF: 0.000637 AC: 34 AN: 53412

Middle Eastern (MID) AF: 0.000868 AC: 5 AN: 5762

European-Non Finnish (NFE) AF: 0.000833 AC: 926 AN: 1111884

Other (OTH) AF: 0.000712 AC: 43 AN: 60384

GnomAD4 genome AF: 0.000625 AC: 95 AN: 152082 Hom.: 0 Cov.: 32 AF XY: 0.000632 AC XY: 47 AN XY: 74356

African (AFR) AF: 0.000145 AC: 6 AN: 41452

American (AMR) AF: 0.000196 AC: 3 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4808

European-Finnish (FIN) AF: 0.000662 AC: 7 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00106 AC: 72 AN: 67994

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000503 Hom.: 0

Bravo AF: 0.000400

EpiCase AF: 0.000927

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	1	Episodic ataxia type 6 (1)
-	-	1	not specified (1)
-	-	1	SLC1A3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.7
DANN	Benign	0.64
PhyloP100		0.052
PromoterAI		0.024	Neutral
Mutation Taster		=96/4	polymorphism

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: rs143791614; hg19: chr5-36608540;