X-118566134-A-T

Position:

• chrX-118566134-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_144658.4(DOCK11):​c.823A>T​(p.Thr275Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: DOCK11 NM_144658.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 0.319

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-118566134-A-T is Pathogenic according to our data. Variant chrX-118566134-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 2499983.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.0452711). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK11	NM_144658.4	c.823A>T	p.Thr275Ser	missense_variant	8/53	ENST00000276202.9	NP_653259.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK11	ENST00000276202.9	c.823A>T	p.Thr275Ser	missense_variant	8/53	1	NM_144658.4	ENSP00000276202.7
DOCK11	ENST00000276204.10	c.823A>T	p.Thr275Ser	missense_variant	8/53	5		ENSP00000276204.6
DOCK11	ENST00000633080.1	c.271A>T	p.Thr91Ser	missense_variant	3/49	5		ENSP00000487829.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Autoinflammatory disease, multisystem, with immune dysregulation, X-linked Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 12, 2023

- -

DOCK11 deficiency Pathogenic:1

Pathogenic, no assertion criteria provided

research

Immunogenetics of Pediatric Autoimmune Diseases, Institut Imagine

Jul 26, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	21
DANN	Benign	0.89
DEOGEN2	Benign	0.0041	.;T;T
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.045	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	.;L;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.010	N;N;.
REVEL	Benign	0.066
Sift	Benign	0.49	T;T;.
Sift4G	Benign	0.41	T;T;T
Polyphen		0.0050	B;B;.
Vest4		0.058
MutPred		0.22		Gain of disorder (P = 0.0638);Gain of disorder (P = 0.0638);.;
MVP		0.27
MPC		0.32
ClinPred		0.17	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.084
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-117700097;