rs12551465

Variant names:

• chr9-4575673-A-G
• rs12551465
• NM_004170.6:c.876-328A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004170.6(SLC1A1):​c.876-328A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 152,068 control chromosomes in the GnomAD database, including 11,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.38 (11687 hom., cov: 32)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.528
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 9-4575673-A-G is Benign according to our data. Variant chr9-4575673-A-G is described in ClinVar as Benign. ClinVar VariationId is 1245469.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.876-328A>G		intron_variant	Intron 8 of 11	ENST00000262352.8	NP_004161.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A1	ENST00000262352.8	c.876-328A>G		intron_variant	Intron 8 of 11	1	NM_004170.6	ENSP00000262352.3
SLC1A1	ENST00000422398.1	c.162-328A>G		intron_variant	Intron 2 of 4	4		ENSP00000414620.1
SPATA6L	ENST00000485616.5	n.*782-21285T>C		intron_variant	Intron 12 of 12	2		ENSP00000420003.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58015 AN: 151950 Hom.: 11691 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.382 AC: 58027 AN: 152068 Hom.: 11687 Cov.: 32 AF XY: 0.382 AC XY: 28431 AN XY: 74348

African (AFR) AF: 0.261 AC: 10835 AN: 41494

American (AMR) AF: 0.429 AC: 6548 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1899 AN: 3468

East Asian (EAS) AF: 0.264 AC: 1366 AN: 5178

South Asian (SAS) AF: 0.487 AC: 2346 AN: 4814

European-Finnish (FIN) AF: 0.364 AC: 3855 AN: 10590

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29722 AN: 67946

Other (OTH) AF: 0.427 AC: 901 AN: 2112

Alfa AF: 0.419 Hom.: 9252

Bravo AF: 0.382

Asia WGS AF: 0.379 AC: 1315 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.4
DANN	Benign	0.86
PhyloP100		-0.53
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: rs12551465; hg19: chr9-4575673;