9-4576851-G-C

Variant names:

• chr9-4576851-G-C
• rs301979
• NM_004170.6:c.1193+88G>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.1193+88G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 1,146,710 control chromosomes in the GnomAD database, including 285,899 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (40520 hom., cov: 33)
  • Exomes 𝑓: 0.70 (245379 hom.)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.160

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=-0.96).
• BP6: Variant 9-4576851-G-C is Benign according to our data. Variant chr9-4576851-G-C is described in ClinVar as [Benign]. Clinvar id is 1226556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.1193+88G>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.1193+88G>C		intron_variant	Intron 10 of 11	1	NM_004170.6	ENSP00000262352.3
SLC1A1	ENST00000422398.1	c.479+88G>C		intron_variant	Intron 4 of 4	4		ENSP00000414620.1
SPATA6L	ENST00000485616.5	n.*782-22463C>G		intron_variant	Intron 12 of 12	2		ENSP00000420003.1

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110861 AN: 152048 Hom.: 40470 Cov.: 33

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.736

GnomAD4 exome AF: 0.701 AC: 697344 AN: 994544 Hom.: 245379 AF XY: 0.698 AC XY: 359115 AN XY: 514538

African (AFR) AF: 0.761 AC: 18471 AN: 24280

American (AMR) AF: 0.775 AC: 34032 AN: 43922

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 16806 AN: 23286

East Asian (EAS) AF: 0.727 AC: 27236 AN: 37460

South Asian (SAS) AF: 0.624 AC: 47694 AN: 76484

European-Finnish (FIN) AF: 0.760 AC: 39440 AN: 51874

Middle Eastern (MID) AF: 0.700 AC: 2314 AN: 3306

European-Non Finnish (NFE) AF: 0.696 AC: 479604 AN: 689226

Other (OTH) AF: 0.710 AC: 31747 AN: 44706

GnomAD4 genome AF: 0.729 AC: 110964 AN: 152166 Hom.: 40520 Cov.: 33 AF XY: 0.729 AC XY: 54252 AN XY: 74388

African (AFR) AF: 0.771 AC: 31998 AN: 41512

American (AMR) AF: 0.753 AC: 11519 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2476 AN: 3468

East Asian (EAS) AF: 0.731 AC: 3789 AN: 5182

South Asian (SAS) AF: 0.614 AC: 2953 AN: 4812

European-Finnish (FIN) AF: 0.767 AC: 8126 AN: 10594

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47796 AN: 67986

Other (OTH) AF: 0.736 AC: 1555 AN: 2114

Alfa AF: 0.610 Hom.: 1687

Bravo AF: 0.736

Asia WGS AF: 0.688 AC: 2391 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

- -

Aug 20, 2019

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	-0.96
CADD	Benign	2.0
DANN	Benign	0.33
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

Publications

LitVar

Other links and lift over

dbSNP: rs301979; hg19: chr9-4576851; COSMIC: COSV52053466;