9-4582843-T-C

Variant names:

• chr9-4582843-T-C
• rs301435
• NM_004170.6:c.1194-195T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004170.6(SLC1A1):​c.1194-195T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,992 control chromosomes in the GnomAD database, including 23,580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.55 (23580 hom., cov: 31)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.861
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 9-4582843-T-C is Benign according to our data. Variant chr9-4582843-T-C is described in ClinVar as [Benign]. Clinvar id is 1294858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.1194-195T>C		intron_variant	Intron 10 of 11	ENST00000262352.8	NP_004161.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A1	ENST00000262352.8	c.1194-195T>C		intron_variant	Intron 10 of 11	1	NM_004170.6	ENSP00000262352.3
SLC1A1	ENST00000422398.1	c.480-2469T>C		intron_variant	Intron 4 of 4	4		ENSP00000414620.1
SPATA6L	ENST00000485616.5	n.*781+17810A>G		intron_variant	Intron 12 of 12	2		ENSP00000420003.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82926 AN: 151874 Hom.: 23530 Cov.: 31

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.543

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.546 AC: 83032 AN: 151992 Hom.: 23580 Cov.: 31 AF XY: 0.553 AC XY: 41068 AN XY: 74290

African (AFR) AF: 0.643 AC: 26641 AN: 41448

American (AMR) AF: 0.644 AC: 9835 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1834 AN: 3464

East Asian (EAS) AF: 0.858 AC: 4439 AN: 5174

South Asian (SAS) AF: 0.502 AC: 2419 AN: 4814

European-Finnish (FIN) AF: 0.537 AC: 5670 AN: 10556

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30534 AN: 67942

Other (OTH) AF: 0.543 AC: 1146 AN: 2112

Alfa AF: 0.492 Hom.: 31651

Bravo AF: 0.564

Asia WGS AF: 0.682 AC: 2371 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.30
DANN	Benign	0.55
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs301435; hg19: chr9-4582843;