Variant X-118566165-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_144658.4(DOCK11):c.854C>T(p.Thr285Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000367 in 1,198,515 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000040 ( 0 hom. 17 hem. )

Consequence

DOCK11
NM_144658.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.04

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031357855).

BS2

High Hemizygotes in GnomAdExome4 at 17 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK11	NM_144658.4 link	c.854C>T	p.Thr285Met	missense_variant	Exon 8 of 53	ENST00000276202.9	NP_653259.3	Q5JSL3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DOCK11	ENST00000276202.9 link	c.854C>T	p.Thr285Met	missense_variant	Exon 8 of 53	1	NM_144658.4	ENSP00000276202.7	Q5JSL3
DOCK11	ENST00000276204.10 link	c.854C>T	p.Thr285Met	missense_variant	Exon 8 of 53	5		ENSP00000276204.6	A6NIW2
DOCK11	ENST00000633080.1 link	c.302C>T	p.Thr101Met	missense_variant	Exon 3 of 49	5		ENSP00000487829.1	A0A0J9YW64

Frequencies

GnomAD3 genomes

AF:

0.00000896

AC:

AN:

111596

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33778

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000374

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000115

AC:

AN:

174341

Hom.:

AF XY:

0.000131

AC XY:

AN XY:

60913

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000455

Gnomad SAS exome

AF:

0.000714

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000126

Gnomad OTH exome

AF:

0.000235

GnomAD4 exome

AF:

0.0000396

AC:

AN:

1086866

Hom.:

Cov.:

AF XY:

0.0000480

AC XY:

AN XY:

354534

show subpopulations

Gnomad4 AFR exome

AF:

0.0000389

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000199

Gnomad4 SAS exome

AF:

0.000385

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000131

Gnomad4 OTH exome

AF:

0.000110

GnomAD4 genome

AF:

0.00000896

AC:

AN:

111649

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33841

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000375

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000869

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000115

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 18, 2024

The c.854C>T (p.T285M) alteration is located in exon 8 (coding exon 8) of the DOCK11 gene. This alteration results from a C to T substitution at nucleotide position 854, causing the threonine (T) at amino acid position 285 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.026

.;T;T

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.81

T;T;T

M_CAP

Benign

0.0083

MetaRNN

Benign

0.031

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

.;L;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.2

N;N;.

REVEL

Benign

0.039

Sift

Benign

0.11

T;T;.

Sift4G

Benign

0.096

T;T;T

Polyphen

0.021

B;B;.

Vest4

0.15

MVP

0.10

MPC

0.37

ClinPred

0.022

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.068

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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