rs12428661

Variant names:

• chr13-98923314-G-A
• rs12428661
• NM_001366683.2:c.474C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-98923314-G-A
• chr13-98923314-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001366683.2(DOCK9):​c.474C>T​(p.Val158Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,612,214 control chromosomes in the GnomAD database, including 23,051 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1851 hom., cov: 33)
  • Exomes 𝑓: 0.17 (21200 hom.)
• Consequence: DOCK9 NM_001366683.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.571

Genes affected

DOCK9 (HGNC:14132): (dedicator of cytokinesis 9) Enables cadherin binding activity. Predicted to be involved in positive regulation of GTPase activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-0.571 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK9	NM_001366683.2	c.474C>T	p.Val158Val	synonymous_variant	Exon 5 of 53	ENST00000682017.1	NP_001353612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK9	ENST00000682017.1	c.474C>T	p.Val158Val	synonymous_variant	Exon 5 of 53		NM_001366683.2	ENSP00000507034.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22616 AN: 152032 Hom.: 1850 Cov.: 33

Gnomad AFR AF: 0.0890

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.173

GnomAD3 exomes AF: 0.181 AC: 45108 AN: 248996 Hom.: 4373 AF XY: 0.181 AC XY: 24395 AN XY: 135080

Gnomad AFR exome AF: 0.0883

Gnomad AMR exome AF: 0.236

Gnomad ASJ exome AF: 0.174

Gnomad EAS exome AF: 0.199

Gnomad SAS exome AF: 0.205

Gnomad FIN exome AF: 0.164

Gnomad NFE exome AF: 0.172

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.167 AC: 244533 AN: 1460064 Hom.: 21200 Cov.: 31 AF XY: 0.169 AC XY: 122546 AN XY: 726410

Gnomad4 AFR exome AF: 0.0849

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.242

Gnomad4 SAS exome AF: 0.204

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.149 AC: 22633 AN: 152150 Hom.: 1851 Cov.: 33 AF XY: 0.149 AC XY: 11115 AN XY: 74384

Gnomad4 AFR AF: 0.0893

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.172

Alfa AF: 0.146 Hom.: 941

Bravo AF: 0.148

EpiCase AF: 0.173

EpiControl AF: 0.170

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.9
DANN	Benign	0.68

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: rs12428661; hg19: chr13-99575568; COSMIC: COSV59623639;