5-36686090-G-T

Variant names:

• chr5-36686090-G-T
• rs549164007
• NM_004172.5:c.1450G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004172.5(SLC1A3):​c.1450G>T​(p.Val484Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V484I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC1A3 NM_004172.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.91
• Publications: 1 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.862

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.1450G>T	p.Val484Leu	missense	Exon 10 of 10	NP_004163.3
	SLC1A3	NM_001438458.1		c.1591G>T	p.Val531Leu	missense	Exon 11 of 11	NP_001425387.1
	SLC1A3	NM_001438454.1		c.1450G>T	p.Val484Leu	missense	Exon 11 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.1450G>T	p.Val484Leu	missense	Exon 10 of 10	ENSP00000265113.4
	SLC1A3	ENST00000381918.4	TSL:1	c.1450G>T	p.Val484Leu	missense	Exon 10 of 10	ENSP00000371343.4
	SLC1A3	ENST00000680232.1		c.1591G>T	p.Val531Leu	missense	Exon 11 of 11	ENSP00000506207.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.97
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.055	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	0.26	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		9.9
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-2.8	D
REVEL	Pathogenic	0.65
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.71		Gain of methylation at R479 (P = 0.1715)
MVP		0.87
MPC		1.3
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.92
gMVP		0.99
Mutation Taster		=26/74	disease causing

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: rs549164007; hg19: chr5-36686192;