chrX-118495995-C-T

Variant names:

• chrX-118495995-C-T
• rs779717069
• NM_144658.4:c.24C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_144658.4(DOCK11):​c.24C>T​(p.Thr8Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,093,055 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000081 (0 hom., 3 hem., cov: 23)
  • Exomes 𝑓: 0.000038 (0 hom. 11 hem.)
• Consequence: DOCK11 NM_144658.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.253
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• autoinflammatory disease, multisystem, with immune dysregulation, X-linked

  Inheritance: XL Classification: STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant X-118495995-C-T is Benign according to our data. Variant chrX-118495995-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2661264.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.253 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 3 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144658.4. 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
	DOCK11	NM_144658.4	MANE Select	c.24C>T	p.Thr8Thr	synonymous	Exon 1 of 53	NP_653259.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK11	ENST00000276202.9	TSL:1 MANE Select	c.24C>T	p.Thr8Thr	synonymous	Exon 1 of 53	ENSP00000276202.7	Q5JSL3
	DOCK11	ENST00000276204.10	TSL:5	c.24C>T	p.Thr8Thr	synonymous	Exon 1 of 53	ENSP00000276204.6	A6NIW2
	DOCK11	ENST00000966546.1		c.24C>T	p.Thr8Thr	synonymous	Exon 1 of 53	ENSP00000636605.1

Frequencies

GnomAD3 genomes AF: 0.0000807 AC: 9 AN: 111520 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000286

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000152

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000765 AC: 4 AN: 52297 AF XY: 0.0000567

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000215

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000377 AC: 37 AN: 981490 Hom.: 0 Cov.: 29 AF XY: 0.0000350 AC XY: 11 AN XY: 314632

African (AFR) AF: 0.00 AC: 0 AN: 20839

American (AMR) AF: 0.00 AC: 0 AN: 20505

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16572

East Asian (EAS) AF: 0.00 AC: 0 AN: 20788

South Asian (SAS) AF: 0.0000223 AC: 1 AN: 44754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24562

Middle Eastern (MID) AF: 0.000292 AC: 1 AN: 3428

European-Non Finnish (NFE) AF: 0.0000431 AC: 34 AN: 789174

Other (OTH) AF: 0.0000245 AC: 1 AN: 40868

GnomAD4 genome AF: 0.0000807 AC: 9 AN: 111565 Hom.: 0 Cov.: 23 AF XY: 0.0000887 AC XY: 3 AN XY: 33833

African (AFR) AF: 0.00 AC: 0 AN: 30836

American (AMR) AF: 0.00 AC: 0 AN: 10713

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.000287 AC: 1 AN: 3482

South Asian (SAS) AF: 0.00 AC: 0 AN: 2706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5968

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 215

European-Non Finnish (NFE) AF: 0.000152 AC: 8 AN: 52791

Other (OTH) AF: 0.00 AC: 0 AN: 1532

Alfa AF: 0.000230 Hom.: 2

Bravo AF: 0.0000793

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.9
DANN	Benign	0.94
PhyloP100		-0.25
PromoterAI		-0.089	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism

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: rs779717069; hg19: chrX-117629958;