rs3087879

chr9-4586808-G-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.*1250G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,088 control chromosomes in the GnomAD database, including 6,542 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6541 hom., cov: 32)
  • Exomes 𝑓: 0.41 (1 hom.)
• Consequence: SLC1A1 NM_004170.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.939

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=-0.84).
• BP6: Variant 9-4586808-G-C is Benign according to our data. Variant chr9-4586808-G-C is described in ClinVar as [Benign]. Clinvar id is 367084.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A1	NM_004170.6	c.*1250G>C		3_prime_UTR_variant	12/12	ENST00000262352.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A1	ENST00000262352.8	c.*1250G>C		3_prime_UTR_variant	12/12	1	NM_004170.6	P1
SPATA6L	ENST00000485616.5	c.*781+13845C>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43145 AN: 151948 Hom.: 6539 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.409 AC: 9 AN: 22 Hom.: 1 Cov.: 0 AF XY: 0.400 AC XY: 4 AN XY: 10

Gnomad4 ASJ exome AF: 0.250

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.284 AC: 43167 AN: 152066 Hom.: 6541 Cov.: 32 AF XY: 0.280 AC XY: 20830 AN XY: 74320

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.322

Alfa AF: 0.302 Hom.: 936

Bravo AF: 0.290

Asia WGS AF: 0.186 AC: 648 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dicarboxylic aminoaciduria Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.6
Dann	Benign	0.63

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: rs3087879; hg19: chr9-4586808;