9-4561596-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004170.6(SLC1A1):c.325+55G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,130,482 control chromosomes in the GnomAD database, including 40,238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (5051 hom., cov: 32)
  • Exomes 𝑓: 0.26 (35187 hom.)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.419

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 9-4561596-G-A is Benign according to our data. Variant chr9-4561596-G-A is described in ClinVar as [Benign]. Clinvar id is 1239990.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A1	NM_004170.6	c.325+55G>A		intron_variant		ENST00000262352.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A1	ENST00000262352.8	c.325+55G>A		intron_variant		1	NM_004170.6	P1
SPATA6L	ENST00000485616.5	c.*782-7208C>T		intron_variant, NMD_transcript_variant		2
SLC1A1	ENST00000490167.1	n.369+55G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37427 AN: 151774 Hom.: 5047 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.259 AC: 253504 AN: 978588 Hom.: 35187 AF XY: 0.254 AC XY: 129028 AN XY: 508368

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.329

Gnomad4 ASJ exome AF: 0.146

Gnomad4 EAS exome AF: 0.461

Gnomad4 SAS exome AF: 0.180

Gnomad4 FIN exome AF: 0.378

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.247 AC: 37443 AN: 151894 Hom.: 5051 Cov.: 32 AF XY: 0.252 AC XY: 18714 AN XY: 74242

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.225

Alfa AF: 0.214 Hom.: 1754

Bravo AF: 0.243

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	11
Dann	Benign	0.76

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: rs10974625; hg19: chr9-4561596; COSMIC: COSV52053421;