16-89280475-C-G

Position:

chr16-89280475-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_013275.6(ANKRD11):c.6067G>C(p.Ala2023Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0403 in 1,602,602 control chromosomes in the GnomAD database, including 1,621 homozygotes. 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 Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 165 hom., cov: 32)

Exomes 𝑓: 0.040 ( 1456 hom. )

Consequence

ANKRD11
NM_013275.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.467

Variant links:

Genes affected

ANKRD11 (HGNC:21316): (ankyrin repeat domain containing 11) This locus encodes an ankryin repeat domain-containing protein. The encoded protein inhibits ligand-dependent activation of transcription. Mutations in this gene have been associated with KBG syndrome, which is characterized by macrodontia, distinctive craniofacial features, short stature, skeletal anomalies, global developmental delay, seizures and intellectual disability. Alternatively spliced transcript variants have been described. Related pseudogenes exist on chromosomes 2 and X. [provided by RefSeq, Jan 2012]

ANKRD11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017634332).

BP6

Variant 16-89280475-C-G is Benign according to our data. Variant chr16-89280475-C-G is described in ClinVar as [Benign]. Clinvar id is 380368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89280475-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ANKRD11	NM_013275.6 linkuse as main transcript	c.6067G>C	p.Ala2023Pro	missense_variant	9/13	ENST00000301030.10	NP_037407.4
ANKRD11	NM_001256182.2 linkuse as main transcript	c.6067G>C	p.Ala2023Pro	missense_variant	10/14		NP_001243111.1
ANKRD11	NM_001256183.2 linkuse as main transcript	c.6067G>C	p.Ala2023Pro	missense_variant	9/13		NP_001243112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD11	ENST00000301030.10 linkuse as main transcript	c.6067G>C	p.Ala2023Pro	missense_variant	9/13	5	NM_013275.6	ENSP00000301030	P1

Frequencies

GnomAD3 genomes

AF:

0.0405

AC:

6165

AN:

152152

Hom.:

165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0311

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0266

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.0645

Gnomad SAS

AF:

0.0157

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0380

Gnomad OTH

AF:

0.0321

GnomAD3 exomes

AF:

0.0456

AC:

9298

AN:

203938

Hom.:

329

AF XY:

0.0437

AC XY:

4969

AN XY:

113748

show subpopulations

Gnomad AFR exome

AF:

0.0386

Gnomad AMR exome

AF:

0.0332

Gnomad ASJ exome

AF:

0.0110

Gnomad EAS exome

AF:

0.0784

Gnomad SAS exome

AF:

0.0105

Gnomad FIN exome

AF:

0.127

Gnomad NFE exome

AF:

0.0415

Gnomad OTH exome

AF:

0.0489

GnomAD4 exome

AF:

0.0403

AC:

58437

AN:

1450332

Hom.:

1456

Cov.:

AF XY:

0.0391

AC XY:

28210

AN XY:

720908

show subpopulations

Gnomad4 AFR exome

AF:

0.0300

Gnomad4 AMR exome

AF:

0.0307

Gnomad4 ASJ exome

AF:

0.0109

Gnomad4 EAS exome

AF:

0.0665

Gnomad4 SAS exome

AF:

0.0117

Gnomad4 FIN exome

AF:

0.122

Gnomad4 NFE exome

AF:

0.0395

Gnomad4 OTH exome

AF:

0.0365

GnomAD4 genome

AF:

0.0405

AC:

6168

AN:

152270

Hom.:

165

Cov.:

AF XY:

0.0440

AC XY:

3277

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0311

Gnomad4 AMR

AF:

0.0265

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.0649

Gnomad4 SAS

AF:

0.0160

Gnomad4 FIN

AF:

0.129

Gnomad4 NFE

AF:

0.0380

Gnomad4 OTH

AF:

0.0317

Alfa

AF:

0.0210

Hom.:

Bravo

AF:

0.0331

TwinsUK

AF:

0.0332

AC:

123

ALSPAC

AF:

0.0361

AC:

139

ESP6500AA

AF:

0.0180

AC:

ESP6500EA

AF:

0.0308

AC:

203

ExAC

AF:

0.0395

AC:

4582

Asia WGS

AF:

0.0420

AC:

146

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 22, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 28, 2017	- -

KBG syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 19, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.59

CADD

Benign

2.9

DANN

Benign

0.90

DEOGEN2

Benign

0.078

T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.61

.;.;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.39

N;N;.

REVEL

Benign

0.0090

Sift

Benign

0.27

T;T;.

Sift4G

Benign

0.30

T;T;.

Polyphen

0.45

B;B;B

Vest4

0.067

MPC

0.16

ClinPred

0.0016

GERP RS

0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

Varity_R

0.093

gMVP

0.088

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