rs3776581

Positions:

• chr5-36661842-A-G
• chr5-36661842-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004172.5(SLC1A3):​c.320-9187A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,132 control chromosomes in the GnomAD database, including 30,996 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 0.62 (30996 hom., cov: 33)
• Consequence: SLC1A3 NM_004172.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A3	NM_004172.5	c.320-9187A>G		intron_variant		ENST00000265113.9	NP_004163.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A3	ENST00000265113.9	c.320-9187A>G		intron_variant		1	NM_004172.5	ENSP00000265113.4

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93575 AN: 152014 Hom.: 30995 Cov.: 33

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.615 AC: 93600 AN: 152132 Hom.: 30996 Cov.: 33 AF XY: 0.618 AC XY: 45926 AN XY: 74368

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.709

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.742

Gnomad4 NFE AF: 0.723

Gnomad4 OTH AF: 0.624

Alfa AF: 0.694 Hom.: 19779

Bravo AF: 0.604

Asia WGS AF: 0.660 AC: 2292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs3776581; hg19: chr5-36661944;