NM_013275.6:c.-60+36029C>T

Variant names:

• chr16-89382255-G-A
• rs3096299
• NM_013275.6:c.-60+36029C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013275.6(ANKRD11):​c.-60+36029C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 151,754 control chromosomes in the GnomAD database, including 23,247 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (23247 hom., cov: 30)
• Consequence: ANKRD11 NM_013275.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435
• Publications: 19 publications found

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

LOC128462377 (HGNC:0):

LOC128462377 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013275.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD11	NM_013275.6	MANE Select	c.-60+36029C>T		intron	N/A	NP_037407.4
	LOC128462377	NM_001416403.1	MANE Select	c.9+36029C>T		intron	N/A	NP_001403332.1
	ANKRD11	NM_001256182.2		c.-60+36029C>T		intron	N/A	NP_001243111.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD11	ENST00000301030.10	TSL:5 MANE Select	c.-60+36029C>T		intron	N/A	ENSP00000301030.4
	ENSG00000288715	ENST00000711617.1	MANE Select	c.9+36029C>T		intron	N/A	ENSP00000518812.1
	ANKRD11	ENST00000378330.7	TSL:1	c.-60+36029C>T		intron	N/A	ENSP00000367581.2

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83586 AN: 151638 Hom.: 23218 Cov.: 30

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.632

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.551 AC: 83663 AN: 151754 Hom.: 23247 Cov.: 30 AF XY: 0.548 AC XY: 40595 AN XY: 74108

African (AFR) AF: 0.517 AC: 21391 AN: 41350

American (AMR) AF: 0.568 AC: 8658 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2391 AN: 3468

East Asian (EAS) AF: 0.592 AC: 3053 AN: 5158

South Asian (SAS) AF: 0.546 AC: 2630 AN: 4816

European-Finnish (FIN) AF: 0.460 AC: 4825 AN: 10488

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38593 AN: 67912

Other (OTH) AF: 0.634 AC: 1335 AN: 2106

Alfa AF: 0.572 Hom.: 73741

Bravo AF: 0.557

Asia WGS AF: 0.594 AC: 2064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.87
DANN	Benign	0.58
PhyloP100		-0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3096299; hg19: chr16-89448663;