9-4561426-T-C

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.233-23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,420,344 control chromosomes in the GnomAD database, including 1,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.051 (552 hom., cov: 32)
  • Exomes 𝑓: 0.011 (534 hom.)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.72

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 9-4561426-T-C is Benign according to our data. Variant chr9-4561426-T-C is described in ClinVar as [Benign]. Clinvar id is 1259249.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A1	NM_004170.6	c.233-23T>C		intron_variant		ENST00000262352.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A1	ENST00000262352.8	c.233-23T>C		intron_variant		1	NM_004170.6	P1
SPATA6L	ENST00000485616.5	c.*782-7038A>G		intron_variant, NMD_transcript_variant		2
SLC1A1	ENST00000490167.1	n.277-23T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 7734 AN: 152132 Hom.: 552 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00885

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00742

Gnomad OTH AF: 0.0325

GnomAD3 exomes AF: 0.0166 AC: 4174 AN: 251304 Hom.: 237 AF XY: 0.0135 AC XY: 1834 AN XY: 135808

Gnomad AFR exome AF: 0.171

Gnomad AMR exome AF: 0.00827

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00180

Gnomad FIN exome AF: 0.00921

Gnomad NFE exome AF: 0.00680

Gnomad OTH exome AF: 0.0124

GnomAD4 exome AF: 0.0110 AC: 13991 AN: 1268094 Hom.: 534 Cov.: 19 AF XY: 0.0100 AC XY: 6439 AN XY: 641506

Gnomad4 AFR exome AF: 0.173

Gnomad4 AMR exome AF: 0.00987

Gnomad4 ASJ exome AF: 0.000440

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00180

Gnomad4 FIN exome AF: 0.00905

Gnomad4 NFE exome AF: 0.00745

Gnomad4 OTH exome AF: 0.0141

GnomAD4 genome AF: 0.0509 AC: 7749 AN: 152250 Hom.: 552 Cov.: 32 AF XY: 0.0496 AC XY: 3691 AN XY: 74432

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.0198

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00885

Gnomad4 NFE AF: 0.00742

Gnomad4 OTH AF: 0.0321

Alfa AF: 0.0158 Hom.: 108

Bravo AF: 0.0565

Asia WGS AF: 0.00953 AC: 34 AN: 3478

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

May 16, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	10
Dann	Benign	0.47

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: rs9407286; hg19: chr9-4561426;