9-4587146-A-G

Position:

• chr9-4587146-A-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.*1588A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,600 control chromosomes in the GnomAD database, including 3,750 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3740 hom., cov: 32)
  • Exomes 𝑓: 0.23 (10 hom.)
• Consequence: SLC1A1 NM_004170.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.02

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=-0.82).
• BP6: Variant 9-4587146-A-G is Benign according to our data. Variant chr9-4587146-A-G is described in ClinVar as [Benign]. Clinvar id is 367090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.*1588A>G		3_prime_UTR_variant	12/12	ENST00000262352.8	NP_004161.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A1	ENST00000262352.8	c.*1588A>G		3_prime_UTR_variant	12/12	1	NM_004170.6	ENSP00000262352.3
SPATA6L	ENST00000485616.5	n.*781+13507T>C		intron_variant		2		ENSP00000420003.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28270 AN: 152052 Hom.: 3739 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.0729

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.233 AC: 100 AN: 430 Hom.: 10 Cov.: 0 AF XY: 0.254 AC XY: 66 AN XY: 260

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.186 AC: 28287 AN: 152170 Hom.: 3740 Cov.: 32 AF XY: 0.198 AC XY: 14723 AN XY: 74370

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.0729

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.160

Alfa AF: 0.143 Hom.: 877

Bravo AF: 0.190

Asia WGS AF: 0.438 AC: 1522 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Dicarboxylic aminoaciduria Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

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	-0.82
CADD	Benign	5.7
DANN	Benign	0.74

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: rs3056; hg19: chr9-4587146;