16-89282307-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_013275.6(ANKRD11):c.4235T>C(p.Ile1412Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000278 in 1,614,104 control chromosomes in the GnomAD database, including 1 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 1 hom. )

Consequence

ANKRD11
NM_013275.6 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.145

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=0.009941012).

BP6

Variant 16-89282307-A-G is Benign according to our data. Variant chr16-89282307-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 377179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89282307-A-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000293 (428/1461892) while in subpopulation NFE AF= 0.000357 (397/1112012). AF 95% confidence interval is 0.000327. There are 1 homozygotes in gnomad4_exome. There are 219 alleles in male gnomad4_exome subpopulation. Median coverage is 36. This position pass quality control queck.

BS2

High AC in GnomAd4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD11	NM_013275.6 link	c.4235T>C	p.Ile1412Thr	missense_variant	Exon 9 of 13	ENST00000301030.10	NP_037407.4	Q6UB99
ANKRD11	NM_001256182.2 link	c.4235T>C	p.Ile1412Thr	missense_variant	Exon 10 of 14		NP_001243111.1	Q6UB99
ANKRD11	NM_001256183.2 link	c.4235T>C	p.Ile1412Thr	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.4235T>C	p.Ile1412Thr	missense_variant	Exon 9 of 13	5	NM_013275.6	ENSP00000301030.4		Q6UB99

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000262

AC:

AN:

251464

Hom.:

AF XY:

0.000302

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000501

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000293

AC:

428

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000301

AC XY:

219

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000357

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000131

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000274

Hom.:

Bravo

AF:

0.000128

ExAC

AF:

0.000338

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 12, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 23, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

KBG syndrome

Benign:1

Oct 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Nov 12, 2018

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely 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. -

ANKRD11-related disorder

Benign:1

Feb 02, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.30

DANN

Benign

0.29

DEOGEN2

Benign

0.062

T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.54

.;.;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.0099

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.27

N;N;.

REVEL

Benign

0.038

Sift

Benign

0.34

T;T;.

Sift4G

Benign

0.75

T;T;.

Polyphen

0.0

B;B;B

Vest4

0.098

MVP

0.13

MPC

0.11

ClinPred

0.019

GERP RS

-2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.022

gMVP

0.0040

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