5-36676059-T-C

Variant names:

• chr5-36676059-T-C
• rs1549627
• NM_004172.5:c.568-833T>C

Variant summary

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

The NM_004172.5(SLC1A3):​c.568-833T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,998 control chromosomes in the GnomAD database, including 19,229 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 0.50 (19229 hom., cov: 32)
• Consequence: SLC1A3 NM_004172.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256
• 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-AS1 (HGNC:56374): (SLC1A3 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A3	NM_004172.5	c.568-833T>C		intron_variant	Intron 5 of 9	ENST00000265113.9	NP_004163.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A3	ENST00000265113.9	c.568-833T>C		intron_variant	Intron 5 of 9	1	NM_004172.5	ENSP00000265113.4

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75236 AN: 151878 Hom.: 19222 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.619

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.495 AC: 75274 AN: 151998 Hom.: 19229 Cov.: 32 AF XY: 0.499 AC XY: 37043 AN XY: 74288

African (AFR) AF: 0.369 AC: 15309 AN: 41434

American (AMR) AF: 0.540 AC: 8245 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1729 AN: 3472

East Asian (EAS) AF: 0.527 AC: 2716 AN: 5150

South Asian (SAS) AF: 0.425 AC: 2046 AN: 4816

European-Finnish (FIN) AF: 0.638 AC: 6738 AN: 10558

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.540 AC: 36732 AN: 67990

Other (OTH) AF: 0.519 AC: 1096 AN: 2112

Alfa AF: 0.518 Hom.: 56612

Bravo AF: 0.487

Asia WGS AF: 0.472 AC: 1643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.9
DANN	Benign	0.89
PhyloP100		-0.26
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: rs1549627; hg19: chr5-36676161;