9-4561374-C-T

Position:

• chr9-4561374-C-T

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.233-75C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 902,958 control chromosomes in the GnomAD database, including 32,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4607 hom., cov: 32)
  • Exomes 𝑓: 0.26 (27442 hom.)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.302

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=-0.8).
• BP6: Variant 9-4561374-C-T is Benign according to our data. Variant chr9-4561374-C-T is described in ClinVar as [Benign]. Clinvar id is 1254104.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.233-75C>T		intron_variant		ENST00000262352.8	NP_004161.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A1	ENST00000262352.8	c.233-75C>T		intron_variant		1	NM_004170.6	ENSP00000262352	P1
SPATA6L	ENST00000485616.5	c.*782-6986G>A		intron_variant, NMD_transcript_variant		2		ENSP00000420003
SLC1A1	ENST00000490167.1	n.277-75C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34606 AN: 151954 Hom.: 4601 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.212

GnomAD4 exome AF: 0.258 AC: 194027 AN: 750882 Hom.: 27442 AF XY: 0.252 AC XY: 101228 AN XY: 401490

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.326

Gnomad4 ASJ exome AF: 0.146

Gnomad4 EAS exome AF: 0.460

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.376

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.228 AC: 34628 AN: 152076 Hom.: 4607 Cov.: 32 AF XY: 0.234 AC XY: 17411 AN XY: 74330

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.210

Alfa AF: 0.234 Hom.: 4288

Bravo AF: 0.220

Asia WGS AF: 0.288 AC: 1000 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	Nov 12, 2018	- -
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	-0.80
CADD	Benign	5.7
DANN	Benign	0.83

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: rs10974624; hg19: chr9-4561374; COSMIC: COSV52053392;