16-89268538-C-T

Variant names:

• chr16-89268538-C-T
• rs1312739816
• NM_013275.6:c.7932G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013275.6(ANKRD11):​c.7932G>A​(p.Val2644Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000757 in 1,320,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V2644V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: ANKRD11 NM_013275.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.380
• Publications: 0 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: Ambry Genetics, G2P, Illumina, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen
• congenital heart defects, multiple types

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000268218 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD11	NM_013275.6	MANE Select	c.7932G>A	p.Val2644Val	synonymous	Exon 13 of 13	NP_037407.4
	ANKRD11	NM_001256182.2		c.7932G>A	p.Val2644Val	synonymous	Exon 14 of 14	NP_001243111.1	Q6UB99
	ANKRD11	NM_001256183.2		c.7932G>A	p.Val2644Val	synonymous	Exon 13 of 13	NP_001243112.1	Q6UB99

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD11	ENST00000301030.10	TSL:5 MANE Select	c.7932G>A	p.Val2644Val	synonymous	Exon 13 of 13	ENSP00000301030.4	Q6UB99
	ANKRD11	ENST00000378330.7	TSL:1	c.7932G>A	p.Val2644Val	synonymous	Exon 14 of 14	ENSP00000367581.2	Q6UB99
	ANKRD11	ENST00000642600.2		c.7932G>A	p.Val2644Val	synonymous	Exon 13 of 13	ENSP00000495226.1	Q6UB99

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.00000659 AC: 1 AN: 151830 AF XY: 0.0000124

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.57e-7 AC: 1 AN: 1320288 Hom.: 0 Cov.: 21 AF XY: 0.00000153 AC XY: 1 AN XY: 652918

African (AFR) AF: 0.00 AC: 0 AN: 30174

American (AMR) AF: 0.00 AC: 0 AN: 35582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24682

East Asian (EAS) AF: 0.00 AC: 0 AN: 35508

South Asian (SAS) AF: 0.00 AC: 0 AN: 77914

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4050

European-Non Finnish (NFE) AF: 9.92e-7 AC: 1 AN: 1008556

Other (OTH) AF: 0.00 AC: 0 AN: 55266

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Benign	0.84
PhyloP100		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1312739816; hg19: chr16-89334946;