NM_013275.6:c.4344T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_013275.6(ANKRD11):c.4344T>C(p.Tyr1448Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 1,614,018 control chromosomes in the GnomAD database, including 987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 70 hom., cov: 32)

Exomes 𝑓: 0.033 ( 917 hom. )

Consequence

ANKRD11
NM_013275.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.91

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

KBG syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, Illumina, ClinGen
congenital heart defects, multiple types
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

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 (BayesDel_noAF=-0.95).

BP6

Variant 16-89282198-A-G is Benign according to our data. Variant chr16-89282198-A-G is described in ClinVar as [Benign]. Clinvar id is 585411.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0248 (3770/152138) while in subpopulation NFE AF = 0.038 (2586/67996). AF 95% confidence interval is 0.0368. There are 70 homozygotes in GnomAd4. There are 1785 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 3770 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD11	NM_013275.6 link	c.4344T>C	p.Tyr1448Tyr	synonymous_variant	Exon 9 of 13	ENST00000301030.10	NP_037407.4	Q6UB99
ANKRD11	NM_001256182.2 link	c.4344T>C	p.Tyr1448Tyr	synonymous_variant	Exon 10 of 14		NP_001243111.1	Q6UB99
ANKRD11	NM_001256183.2 link	c.4344T>C	p.Tyr1448Tyr	synonymous_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.4344T>C	p.Tyr1448Tyr	synonymous_variant	Exon 9 of 13	5	NM_013275.6	ENSP00000301030.4		Q6UB99

Frequencies

GnomAD3 genomes

AF:

0.0248

AC:

3773

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00696

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0238

Gnomad ASJ

AF:

0.0219

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0158

Gnomad FIN

AF:

0.0267

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0380

Gnomad OTH

AF:

0.0325

GnomAD2 exomes

AF:

0.0277

AC:

6967

AN:

251428

AF XY:

0.0283

show subpopulations

Gnomad AFR exome

AF:

0.00671

Gnomad AMR exome

AF:

0.0197

Gnomad ASJ exome

AF:

0.0254

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.0281

Gnomad NFE exome

AF:

0.0399

Gnomad OTH exome

AF:

0.0309

GnomAD4 exome

AF:

0.0333

AC:

48734

AN:

1461880

Hom.:

917

Cov.:

AF XY:

0.0330

AC XY:

24004

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00618

AC:

207

AN:

33480

American (AMR)

AF:

0.0199

AC:

888

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0241

AC:

630

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39700

South Asian (SAS)

AF:

0.0187

AC:

1616

AN:

86258

European-Finnish (FIN)

AF:

0.0289

AC:

1542

AN:

53416

Middle Eastern (MID)

AF:

0.0414

AC:

239

AN:

5766

European-Non Finnish (NFE)

AF:

0.0377

AC:

41924

AN:

1112004

Other (OTH)

AF:

0.0279

AC:

1684

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

3191

6382

9574

12765

15956

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1504

3008

4512

6016

7520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0248

AC:

3770

AN:

152138

Hom.:

Cov.:

AF XY:

0.0240

AC XY:

1785

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.00694

AC:

288

AN:

41492

American (AMR)

AF:

0.0236

AC:

361

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0219

AC:

AN:

3468

East Asian (EAS)

AF:

0.000387

AC:

AN:

5174

South Asian (SAS)

AF:

0.0162

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0267

AC:

283

AN:

10594

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0380

AC:

2586

AN:

67996

Other (OTH)

AF:

0.0322

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

180

360

539

719

899

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0311

Hom.:

Bravo

AF:

0.0240

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.0374

EpiControl

AF:

0.0402

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Sep 01, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

KBG syndrome

Benign:2

Feb 02, 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

- -

Inborn genetic diseases

Benign:1

Mar 13, 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

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.020

(source)

DANN

Benign

0.13

PhyloP100

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over