9-4555305-A-G

Position:

• chr9-4555305-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004170.6(SLC1A1):​c.233-6144A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,238 control chromosomes in the GnomAD database, including 1,164 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 0.10 (1164 hom., cov: 32)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.233-6144A>G		intron_variant		ENST00000262352.8	NP_004161.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A1	ENST00000262352.8	c.233-6144A>G		intron_variant		1	NM_004170.6	ENSP00000262352.3
SPATA6L	ENST00000485616.5	n.*782-917T>C		intron_variant		2		ENSP00000420003.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15743 AN: 152120 Hom.: 1159 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0629

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0526

Gnomad FIN AF: 0.0340

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0770

Gnomad OTH AF: 0.0889

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

GnomAD4 genome AF: 0.104 AC: 15774 AN: 152238 Hom.: 1164 Cov.: 32 AF XY: 0.0997 AC XY: 7421 AN XY: 74446

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.0627

Gnomad4 ASJ AF: 0.0677

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0537

Gnomad4 FIN AF: 0.0340

Gnomad4 NFE AF: 0.0770

Gnomad4 OTH AF: 0.0880

Alfa AF: 0.0825 Hom.: 883

Bravo AF: 0.110

Asia WGS AF: 0.0440 AC: 151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.17
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7856675; hg19: chr9-4555305;