rs10974620

Variant names:

• chr9-4557296-C-G
• rs10974620
• NM_004170.6:c.233-4153C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-4557296-C-G
• chr9-4557296-C-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.233-4153C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,122 control chromosomes in the GnomAD database, including 4,865 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 0.24 (4865 hom., cov: 32)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.233-4153C>G		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.233-4153C>G		intron_variant	Intron 2 of 11	1	NM_004170.6	ENSP00000262352.3
SPATA6L	ENST00000485616.5	n.*782-2908G>C		intron_variant	Intron 12 of 12	2		ENSP00000420003.1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37215 AN: 152004 Hom.: 4854 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.245 AC: 37248 AN: 152122 Hom.: 4865 Cov.: 32 AF XY: 0.249 AC XY: 18526 AN XY: 74364

African (AFR) AF: 0.220 AC: 9138 AN: 41528

American (AMR) AF: 0.280 AC: 4284 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 446 AN: 3466

East Asian (EAS) AF: 0.456 AC: 2360 AN: 5172

South Asian (SAS) AF: 0.194 AC: 934 AN: 4818

European-Finnish (FIN) AF: 0.339 AC: 3582 AN: 10568

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15803 AN: 67974

Other (OTH) AF: 0.222 AC: 468 AN: 2110

Alfa AF: 0.122 Hom.: 218

Bravo AF: 0.244

Asia WGS AF: 0.286 AC: 993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.0
DANN	Benign	0.64
PhyloP100		0.25
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: rs10974620; hg19: chr9-4557296;