Variant chrX-118546056-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_144658.4(DOCK11):c.498G>C(p.Val166Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,205,340 control chromosomes in the GnomAD database, including 17 homozygotes. There are 412 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0071 ( 12 hom., 198 hem., cov: 21)

Exomes 𝑓: 0.00071 ( 5 hom. 214 hem. )

Consequence

DOCK11
NM_144658.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.795

Variant links:

Genes affected

DOCK11 (HGNC:23483): (dedicator of cytokinesis 11) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in several processes, including marginal zone B cell differentiation; positive regulation of GTPase activity; and positive regulation of filopodium assembly. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

DOCK11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant X-118546056-G-C is Benign according to our data. Variant chrX-118546056-G-C is described in ClinVar as [Benign]. Clinvar id is 790798.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.795 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00707 (779/110136) while in subpopulation AFR AF= 0.0248 (748/30198). AF 95% confidence interval is 0.0233. There are 12 homozygotes in gnomad4. There are 198 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK11	NM_144658.4 linkuse as main transcript	c.498G>C	p.Val166Val	synonymous_variant	6/53	ENST00000276202.9	NP_653259.3	Q5JSL3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK11	ENST00000276202.9 linkuse as main transcript	c.498G>C	p.Val166Val	synonymous_variant	6/53	1	NM_144658.4	ENSP00000276202.7		Q5JSL3
DOCK11	ENST00000276204.10 linkuse as main transcript	c.498G>C	p.Val166Val	synonymous_variant	6/53	5		ENSP00000276204.6		A6NIW2

Frequencies

GnomAD3 genomes

AF:

0.00706

AC:

777

AN:

110092

Hom.:

Cov.:

AF XY:

0.00612

AC XY:

198

AN XY:

32342

show subpopulations

Gnomad AFR

AF:

0.0248

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00225

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00427

Gnomad NFE

AF:

0.0000378

Gnomad OTH

AF:

0.00341

GnomAD3 exomes

AF:

0.00199

AC:

363

AN:

182494

Hom.:

AF XY:

0.00121

AC XY:

AN XY:

67000

show subpopulations

Gnomad AFR exome

AF:

0.0241

Gnomad AMR exome

AF:

0.00158

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.000445

GnomAD4 exome

AF:

0.000713

AC:

781

AN:

1095204

Hom.:

Cov.:

AF XY:

0.000593

AC XY:

214

AN XY:

360684

show subpopulations

Gnomad4 AFR exome

AF:

0.0241

Gnomad4 AMR exome

AF:

0.00171

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000372

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000357

Gnomad4 OTH exome

AF:

0.00165

GnomAD4 genome

AF:

0.00707

AC:

779

AN:

110136

Hom.:

Cov.:

AF XY:

0.00611

AC XY:

198

AN XY:

32396

show subpopulations

Gnomad4 AFR

AF:

0.0248

Gnomad4 AMR

AF:

0.00224

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000378

Gnomad4 OTH

AF:

0.00336

Alfa

AF:

0.00277

Hom.:

Bravo

AF:

0.00836

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

9.9

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over