chr16-89281630-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_013275.6(ANKRD11):c.4912C>G(p.Pro1638Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 1,614,110 control chromosomes in the GnomAD database, including 2,628 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1638S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.038 ( 317 hom., cov: 32)

Exomes 𝑓: 0.023 ( 2311 hom. )

Consequence

ANKRD11
NM_013275.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.03

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054450333).

BP6

Variant 16-89281630-G-C is Benign according to our data. Variant chr16-89281630-G-C is described in ClinVar as [Benign]. Clinvar id is 587810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89281630-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD11	NM_013275.6 link	c.4912C>G	p.Pro1638Ala	missense_variant	Exon 9 of 13	ENST00000301030.10	NP_037407.4	Q6UB99
ANKRD11	NM_001256182.2 link	c.4912C>G	p.Pro1638Ala	missense_variant	Exon 10 of 14		NP_001243111.1	Q6UB99
ANKRD11	NM_001256183.2 link	c.4912C>G	p.Pro1638Ala	missense_variant	Exon 9 of 13		NP_001243112.1	Q6UB99

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD11	ENST00000301030.10 link	c.4912C>G	p.Pro1638Ala	missense_variant	Exon 9 of 13	5	NM_013275.6	ENSP00000301030.4		Q6UB99

Frequencies

GnomAD3 genomes

AF:

0.0374

AC:

5685

AN:

152112

Hom.:

315

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0386

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0722

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.249

Gnomad SAS

AF:

0.146

Gnomad FIN

AF:

0.0548

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00457

Gnomad OTH

AF:

0.0368

GnomAD2 exomes

AF:

0.0588

AC:

14781

AN:

251180

AF XY:

0.0590

show subpopulations

Gnomad AFR exome

AF:

0.0383

Gnomad AMR exome

AF:

0.0903

Gnomad ASJ exome

AF:

0.00675

Gnomad EAS exome

AF:

0.265

Gnomad FIN exome

AF:

0.0531

Gnomad NFE exome

AF:

0.00528

Gnomad OTH exome

AF:

0.0436

GnomAD4 exome

AF:

0.0228

AC:

33369

AN:

1461882

Hom.:

2311

Cov.:

AF XY:

0.0256

AC XY:

18625

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0383

AC:

1281

AN:

33480

American (AMR)

AF:

0.0904

AC:

4044

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

158

AN:

26136

East Asian (EAS)

AF:

0.211

AC:

8391

AN:

39700

South Asian (SAS)

AF:

0.130

AC:

11187

AN:

86256

European-Finnish (FIN)

AF:

0.0536

AC:

2861

AN:

53414

Middle Eastern (MID)

AF:

0.0300

AC:

173

AN:

5768

European-Non Finnish (NFE)

AF:

0.00256

AC:

2851

AN:

1112010

Other (OTH)

AF:

0.0401

AC:

2423

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

2139

4278

6418

8557

10696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0375

AC:

5709

AN:

152228

Hom.:

317

Cov.:

AF XY:

0.0446

AC XY:

3321

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0389

AC:

1617

AN:

41532

American (AMR)

AF:

0.0724

AC:

1107

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

AN:

3472

East Asian (EAS)

AF:

0.248

AC:

1281

AN:

5168

South Asian (SAS)

AF:

0.145

AC:

701

AN:

4822

European-Finnish (FIN)

AF:

0.0548

AC:

581

AN:

10608

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00457

AC:

311

AN:

68012

Other (OTH)

AF:

0.0416

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

265

530

796

1061

1326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0162

Hom.:

166

Bravo

AF:

0.0379

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.0291

AC:

128

ESP6500EA

AF:

0.00419

AC:

ExAC

AF:

0.0568

AC:

6899

Asia WGS

AF:

0.192

AC:

667

AN:

3478

EpiCase

AF:

0.00496

EpiControl

AF:

0.00539

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

KBG syndrome

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

May 05, 2021

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Mar 24, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.26

T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.68

.;.;T

MetaRNN

Benign

0.0054

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L;L

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.5

N;N;.

REVEL

Benign

0.026

Sift

Benign

0.079

T;T;.

Sift4G

Benign

0.34

T;T;.

Polyphen

0.0010

B;B;B

Vest4

0.041

MPC

0.095

ClinPred

0.020

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.029

gMVP

0.0027

Mutation Taster

=99/1

polymorphism (auto)

(source)

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.

chr16-89281630-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over