chr9-4576451-T-A

Variant names:

• chr9-4576451-T-A
• rs2072657
• NM_004170.6:c.999-118T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004170.6(SLC1A1):​c.999-118T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000438 in 685,592 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377
• Publications: 12 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.999-118T>A		intron_variant	Intron 9 of 11	ENST00000262352.8	NP_004161.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A1	ENST00000262352.8	c.999-118T>A		intron_variant	Intron 9 of 11	1	NM_004170.6	ENSP00000262352.3
SLC1A1	ENST00000422398.1	c.285-118T>A		intron_variant	Intron 3 of 4	4		ENSP00000414620.1
SPATA6L	ENST00000485616.5	n.*782-22063A>T		intron_variant	Intron 12 of 12	2		ENSP00000420003.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000438 AC: 3 AN: 685592 Hom.: 0 AF XY: 0.00000548 AC XY: 2 AN XY: 364896

African (AFR) AF: 0.00 AC: 0 AN: 18200

American (AMR) AF: 0.00 AC: 0 AN: 35328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20670

East Asian (EAS) AF: 0.00 AC: 0 AN: 34632

South Asian (SAS) AF: 0.0000304 AC: 2 AN: 65738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4034

European-Non Finnish (NFE) AF: 0.00000237 AC: 1 AN: 422816

Other (OTH) AF: 0.00 AC: 0 AN: 34906

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 7419

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.42
PhyloP100		-0.38

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: rs2072657; hg19: chr9-4576451;