chr5-36672142-T-C

Variant names:

• chr5-36672142-T-C
• rs2269271
• NM_004172.5:c.524+909T>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.524+909T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,950 control chromosomes in the GnomAD database, including 14,189 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 0.43 (14189 hom., cov: 32)
• Consequence: SLC1A3 NM_004172.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• 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-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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A3	NM_004172.5	MANE Select	c.524+909T>C		intron	N/A	NP_004163.3
	SLC1A3	NM_001438458.1		c.524+909T>C		intron	N/A	NP_001425387.1
	SLC1A3	NM_001438454.1		c.524+909T>C		intron	N/A	NP_001425383.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A3	ENST00000265113.9	TSL:1 MANE Select	c.524+909T>C		intron	N/A	ENSP00000265113.4	P43003-1
	SLC1A3	ENST00000381918.4	TSL:1	c.524+909T>C		intron	N/A	ENSP00000371343.4	P43003-1
	SLC1A3	ENST00000680232.1		c.524+909T>C		intron	N/A	ENSP00000506207.1	A0A7P0TAG7

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65328 AN: 151830 Hom.: 14184 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.430 AC: 65358 AN: 151950 Hom.: 14189 Cov.: 32 AF XY: 0.430 AC XY: 31966 AN XY: 74266

African (AFR) AF: 0.371 AC: 15378 AN: 41412

American (AMR) AF: 0.473 AC: 7224 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1290 AN: 3470

East Asian (EAS) AF: 0.536 AC: 2764 AN: 5160

South Asian (SAS) AF: 0.413 AC: 1987 AN: 4816

European-Finnish (FIN) AF: 0.492 AC: 5203 AN: 10570

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30038 AN: 67932

Other (OTH) AF: 0.432 AC: 913 AN: 2112

Alfa AF: 0.435 Hom.: 7465

Bravo AF: 0.432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.46
PhyloP100		-1.5
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: rs2269271; hg19: chr5-36672244;