9-4576451-T-G

Position:

• chr9-4576451-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004170.6(SLC1A1):​c.999-118T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 837,180 control chromosomes in the GnomAD database, including 37,810 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6081 hom., cov: 33)
  • Exomes 𝑓: 0.30 (31729 hom.)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.377

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 9-4576451-T-G is Benign according to our data. Variant chr9-4576451-T-G is described in ClinVar as [Benign]. Clinvar id is 1231703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.999-118T>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.999-118T>G		intron_variant		1	NM_004170.6	ENSP00000262352.3
SLC1A1	ENST00000422398.1	c.285-118T>G		intron_variant		4		ENSP00000414620.1
SPATA6L	ENST00000485616.5	n.*782-22063A>C		intron_variant		2		ENSP00000420003.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42619 AN: 152036 Hom.: 6075 Cov.: 33

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.269

GnomAD4 exome AF: 0.301 AC: 206216 AN: 685026 Hom.: 31729 AF XY: 0.305 AC XY: 111348 AN XY: 364602

Gnomad4 AFR exome AF: 0.243

Gnomad4 AMR exome AF: 0.291

Gnomad4 ASJ exome AF: 0.257

Gnomad4 EAS exome AF: 0.296

Gnomad4 SAS exome AF: 0.371

Gnomad4 FIN exome AF: 0.242

Gnomad4 NFE exome AF: 0.304

Gnomad4 OTH exome AF: 0.290

GnomAD4 genome AF: 0.280 AC: 42648 AN: 152154 Hom.: 6081 Cov.: 33 AF XY: 0.279 AC XY: 20750 AN XY: 74400

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.270

Alfa AF: 0.286 Hom.: 4878

Bravo AF: 0.279

Asia WGS AF: 0.330 AC: 1151 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.4
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs2072657; hg19: chr9-4576451; COSMIC: COSV52050745;