9-4576680-T-C

Variant names:

• chr9-4576680-T-C
• rs301430
• NM_004170.6:c.1110T>C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_004170.6(SLC1A1):​c.1110T>C​(p.Thr370Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 1,613,394 control chromosomes in the GnomAD database, including 91,370 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (12023 hom., cov: 33)
  • Exomes 𝑓: 0.32 (79347 hom.)
• Consequence: SLC1A1 NM_004170.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -6.15
• Publications: 51 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.161).
• BP6: Variant 9-4576680-T-C is Benign according to our data. Variant chr9-4576680-T-C is described in ClinVar as Benign. ClinVar VariationId is 367052.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.15 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004170.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A1	NM_004170.6	MANE Select	c.1110T>C	p.Thr370Thr	synonymous	Exon 10 of 12	NP_004161.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A1	ENST00000262352.8	TSL:1 MANE Select	c.1110T>C	p.Thr370Thr	synonymous	Exon 10 of 12	ENSP00000262352.3	P43005
	SLC1A1	ENST00000931882.1		c.1002T>C	p.Thr334Thr	synonymous	Exon 9 of 11	ENSP00000601941.1
	SLC1A1	ENST00000954075.1		c.969T>C	p.Thr323Thr	synonymous	Exon 9 of 11	ENSP00000624134.1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57950 AN: 151922 Hom.: 11979 Cov.: 33

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.335

GnomAD2 exomes AF: 0.363 AC: 91366 AN: 251418 AF XY: 0.357

Gnomad AFR exome AF: 0.508

Gnomad AMR exome AF: 0.382

Gnomad ASJ exome AF: 0.222

Gnomad EAS exome AF: 0.610

Gnomad FIN exome AF: 0.456

Gnomad NFE exome AF: 0.292

Gnomad OTH exome AF: 0.329

GnomAD4 exome AF: 0.321 AC: 468653 AN: 1461354 Hom.: 79347 Cov.: 39 AF XY: 0.320 AC XY: 232990 AN XY: 726974

African (AFR) AF: 0.506 AC: 16923 AN: 33464

American (AMR) AF: 0.380 AC: 17008 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 5804 AN: 26134

East Asian (EAS) AF: 0.605 AC: 24031 AN: 39698

South Asian (SAS) AF: 0.365 AC: 31467 AN: 86244

European-Finnish (FIN) AF: 0.454 AC: 24255 AN: 53420

Middle Eastern (MID) AF: 0.217 AC: 1251 AN: 5766

European-Non Finnish (NFE) AF: 0.295 AC: 328282 AN: 1111534

Other (OTH) AF: 0.325 AC: 19632 AN: 60372

GnomAD4 genome AF: 0.382 AC: 58042 AN: 152040 Hom.: 12023 Cov.: 33 AF XY: 0.388 AC XY: 28831 AN XY: 74318

African (AFR) AF: 0.510 AC: 21149 AN: 41484

American (AMR) AF: 0.354 AC: 5403 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 792 AN: 3464

East Asian (EAS) AF: 0.599 AC: 3083 AN: 5146

South Asian (SAS) AF: 0.387 AC: 1863 AN: 4818

European-Finnish (FIN) AF: 0.463 AC: 4896 AN: 10568

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.293 AC: 19885 AN: 67978

Other (OTH) AF: 0.338 AC: 712 AN: 2106

Alfa AF: 0.320 Hom.: 38621

Bravo AF: 0.381

Asia WGS AF: 0.505 AC: 1757 AN: 3478

EpiCase AF: 0.277

EpiControl AF: 0.273

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Dicarboxylic aminoaciduria (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0050
DANN	Benign	0.37
PhyloP100		-6.1
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: rs301430; hg19: chr9-4576680; COSMIC: COSV52051461;