9-4582082-C-T

Variant names:

• chr9-4582082-C-T
• rs301434
• NM_004170.6:c.1194-956C>T

Variant summary

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

The NM_004170.6(SLC1A1):​c.1194-956C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 152,154 control chromosomes in the GnomAD database, including 22,353 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 0.53 (22353 hom., cov: 32)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 18 publications found

Genes affected

SLC1A1 (HGNC:10939): (solute carrier family 1 member 1) This gene encodes a member of the high-affinity glutamate transporters that play an essential role in transporting glutamate across plasma membranes. In brain, these transporters are crucial in terminating the postsynaptic action of the neurotransmitter glutamate, and in maintaining extracellular glutamate concentrations below neurotoxic levels. This transporter also transports aspartate, and mutations in this gene are thought to cause dicarboxylicamino aciduria, also known as glutamate-aspartate transport defect. [provided by RefSeq, Mar 2010]

SPATA6L (HGNC:25472): (spermatogenesis associated 6 like) Predicted to enable myosin light chain binding activity. Predicted to be involved in spermatogenesis. Predicted to be located in sperm connecting piece. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.1194-956C>T		intron_variant	Intron 10 of 11	ENST00000262352.8	NP_004161.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A1	ENST00000262352.8	c.1194-956C>T		intron_variant	Intron 10 of 11	1	NM_004170.6	ENSP00000262352.3
SLC1A1	ENST00000422398.1	c.480-3230C>T		intron_variant	Intron 4 of 4	4		ENSP00000414620.1
SPATA6L	ENST00000485616.5	n.*781+18571G>A		intron_variant	Intron 12 of 12	2		ENSP00000420003.1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80835 AN: 152036 Hom.: 22308 Cov.: 32

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.532 AC: 80935 AN: 152154 Hom.: 22353 Cov.: 32 AF XY: 0.539 AC XY: 40067 AN XY: 74378

African (AFR) AF: 0.610 AC: 25304 AN: 41494

American (AMR) AF: 0.634 AC: 9699 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1770 AN: 3470

East Asian (EAS) AF: 0.855 AC: 4426 AN: 5178

South Asian (SAS) AF: 0.488 AC: 2353 AN: 4818

European-Finnish (FIN) AF: 0.527 AC: 5574 AN: 10584

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.444 AC: 30167 AN: 68004

Other (OTH) AF: 0.536 AC: 1131 AN: 2112

Alfa AF: 0.488 Hom.: 19898

Bravo AF: 0.548

Asia WGS AF: 0.671 AC: 2331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.012
DANN	Benign	0.52
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: rs301434; hg19: chr9-4582082;