chr16-89282969-G-C

Variant names:

• chr16-89282969-G-C
• rs62000377
• NM_013275.6:c.3573C>G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_013275.6(ANKRD11):​c.3573C>G​(p.Ala1191Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0391 in 1,612,760 control chromosomes in the GnomAD database, including 1,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (147 hom., cov: 32)
  • Exomes 𝑓: 0.040 (1440 hom.)
• Consequence: ANKRD11 NM_013275.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -3.69

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-89282969-G-C is Benign according to our data. Variant chr16-89282969-G-C is described in ClinVar as [Benign]. Clinvar id is 380365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89282969-G-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-3.69 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD11	NM_013275.6	c.3573C>G	p.Ala1191Ala	synonymous_variant	Exon 9 of 13	ENST00000301030.10	NP_037407.4
ANKRD11	NM_001256182.2	c.3573C>G	p.Ala1191Ala	synonymous_variant	Exon 10 of 14		NP_001243111.1
ANKRD11	NM_001256183.2	c.3573C>G	p.Ala1191Ala	synonymous_variant	Exon 9 of 13		NP_001243112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD11	ENST00000301030.10	c.3573C>G	p.Ala1191Ala	synonymous_variant	Exon 9 of 13	5	NM_013275.6	ENSP00000301030.4

Frequencies

GnomAD3 genomes AF: 0.0339 AC: 5120 AN: 151192 Hom.: 147 Cov.: 32

Gnomad AFR AF: 0.00730

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0250

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.0641

Gnomad SAS AF: 0.0160

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.0382

Gnomad OTH AF: 0.0255

GnomAD3 exomes AF: 0.0401 AC: 10055 AN: 250702 Hom.: 366 AF XY: 0.0393 AC XY: 5333 AN XY: 135690

Gnomad AFR exome AF: 0.00736

Gnomad AMR exome AF: 0.0291

Gnomad ASJ exome AF: 0.0103

Gnomad EAS exome AF: 0.0668

Gnomad SAS exome AF: 0.00960

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.0382

Gnomad OTH exome AF: 0.0433

GnomAD4 exome AF: 0.0396 AC: 57861 AN: 1461448 Hom.: 1440 Cov.: 37 AF XY: 0.0386 AC XY: 28045 AN XY: 727052

Gnomad4 AFR exome AF: 0.00624

Gnomad4 AMR exome AF: 0.0298

Gnomad4 ASJ exome AF: 0.0113

Gnomad4 EAS exome AF: 0.0627

Gnomad4 SAS exome AF: 0.0116

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.0395

Gnomad4 OTH exome AF: 0.0352

GnomAD4 genome AF: 0.0338 AC: 5121 AN: 151312 Hom.: 147 Cov.: 32 AF XY: 0.0376 AC XY: 2777 AN XY: 73858

Gnomad4 AFR AF: 0.00728

Gnomad4 AMR AF: 0.0249

Gnomad4 ASJ AF: 0.00980

Gnomad4 EAS AF: 0.0644

Gnomad4 SAS AF: 0.0162

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.0382

Gnomad4 OTH AF: 0.0252

Alfa AF: 0.0248 Hom.: 23

Bravo AF: 0.0252

Asia WGS AF: 0.0410 AC: 142 AN: 3478

EpiCase AF: 0.0307

EpiControl AF: 0.0293

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Sep 22, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Feb 16, 2024

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

Inborn genetic diseases Benign:1

Apr 19, 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. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.011
DANN	Benign	0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs62000377; hg19: chr16-89349377; COSMIC: COSV56357490; COSMIC: COSV56357490;