rs3780413

Variant names:

• chr9-4567353-C-G
• rs3780413
• NM_004170.6:c.484-316C>G

Variant summary

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

The NM_004170.6(SLC1A1):​c.484-316C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 152,100 control chromosomes in the GnomAD database, including 27,913 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 0.58 (27913 hom., cov: 33)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267
• Publications: 13 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.484-316C>G		intron_variant	Intron 5 of 11	ENST00000262352.8	NP_004161.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A1	ENST00000262352.8	c.484-316C>G		intron_variant	Intron 5 of 11	1	NM_004170.6	ENSP00000262352.3
SPATA6L	ENST00000485616.5	n.*782-12965G>C		intron_variant	Intron 12 of 12	2		ENSP00000420003.1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88392 AN: 151982 Hom.: 27919 Cov.: 33

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.618

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

GnomAD4 genome AF: 0.581 AC: 88411 AN: 152100 Hom.: 27913 Cov.: 33 AF XY: 0.589 AC XY: 43829 AN XY: 74350

African (AFR) AF: 0.309 AC: 12813 AN: 41496

American (AMR) AF: 0.687 AC: 10506 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2374 AN: 3472

East Asian (EAS) AF: 0.728 AC: 3768 AN: 5176

South Asian (SAS) AF: 0.654 AC: 3154 AN: 4820

European-Finnish (FIN) AF: 0.742 AC: 7848 AN: 10574

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45913 AN: 67968

Other (OTH) AF: 0.617 AC: 1305 AN: 2114

Alfa AF: 0.610 Hom.: 3673

Bravo AF: 0.569

Asia WGS AF: 0.665 AC: 2311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.23
DANN	Benign	0.59
PhyloP100		-0.27
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: rs3780413; hg19: chr9-4567353;