9-4561651-G-A

Position:

• chr9-4561651-G-A

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.325+110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 778,764 control chromosomes in the GnomAD database, including 27,619 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4586 hom., cov: 32)
  • Exomes 𝑓: 0.26 (23033 hom.)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.365

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=-0.91).
• BP6: Variant 9-4561651-G-A is Benign according to our data. Variant chr9-4561651-G-A is described in ClinVar as [Benign]. Clinvar id is 1262562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.325+110G>A		intron_variant		ENST00000262352.8	NP_004161.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A1	ENST00000262352.8	c.325+110G>A		intron_variant		1	NM_004170.6	ENSP00000262352	P1
SPATA6L	ENST00000485616.5	c.*782-7263C>T		intron_variant, NMD_transcript_variant		2		ENSP00000420003
SLC1A1	ENST00000490167.1	n.369+110G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34443 AN: 151870 Hom.: 4581 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.212

GnomAD4 exome AF: 0.258 AC: 162015 AN: 626774 Hom.: 23033 AF XY: 0.252 AC XY: 85900 AN XY: 341520

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.326

Gnomad4 ASJ exome AF: 0.147

Gnomad4 EAS exome AF: 0.461

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.378

Gnomad4 NFE exome AF: 0.249

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.227 AC: 34463 AN: 151990 Hom.: 4586 Cov.: 32 AF XY: 0.233 AC XY: 17325 AN XY: 74282

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.210

Alfa AF: 0.136 Hom.: 263

Bravo AF: 0.219

Asia WGS AF: 0.288 AC: 1001 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.54

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: rs1805311; hg19: chr9-4561651; COSMIC: COSV52053433;