NM_004170.6:c.233-5876C>T

Variant names:

• chr9-4555573-C-T
• rs3780415
• NM_004170.6:c.233-5876C>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.233-5876C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 152,076 control chromosomes in the GnomAD database, including 21,491 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 0.49 (21491 hom., cov: 33)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.877
• Publications: 6 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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.233-5876C>T		intron_variant	Intron 2 of 11	ENST00000262352.8	NP_004161.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A1	ENST00000262352.8	c.233-5876C>T		intron_variant	Intron 2 of 11	1	NM_004170.6	ENSP00000262352.3
SPATA6L	ENST00000485616.5	n.*782-1185G>A		intron_variant	Intron 12 of 12	2		ENSP00000420003.1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73899 AN: 151958 Hom.: 21493 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.486 AC: 73927 AN: 152076 Hom.: 21491 Cov.: 33 AF XY: 0.493 AC XY: 36647 AN XY: 74354

African (AFR) AF: 0.159 AC: 6595 AN: 41474

American (AMR) AF: 0.511 AC: 7811 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1866 AN: 3466

East Asian (EAS) AF: 0.843 AC: 4357 AN: 5166

South Asian (SAS) AF: 0.653 AC: 3144 AN: 4816

European-Finnish (FIN) AF: 0.644 AC: 6816 AN: 10588

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.612 AC: 41570 AN: 67966

Other (OTH) AF: 0.506 AC: 1069 AN: 2114

Alfa AF: 0.560 Hom.: 81310

Bravo AF: 0.461

Asia WGS AF: 0.679 AC: 2360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.2
DANN	Benign	0.74
PhyloP100		-0.88
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: rs3780415; hg19: chr9-4555573; COSMIC: COSV52051397; COSMIC: COSV52051397;