16-89268253-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_013275.6(ANKRD11):c.*225C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00061 (0 hom., cov: 9)
  • Exomes 𝑓: 0.00098 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD11 NM_013275.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.821

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 16-89268253-G-A is Benign according to our data. Variant chr16-89268253-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1189812.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000981 (215/219238) while in subpopulation MID AF= 0.00459 (4/872). AF 95% confidence interval is 0.00157. There are 2 homozygotes in gnomad4_exome. There are 125 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAdExome at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD11	NM_013275.6	c.*225C>T		3_prime_UTR_variant	13/13	ENST00000301030.10
ANKRD11	NM_001256182.2	c.*225C>T		3_prime_UTR_variant	14/14
ANKRD11	NM_001256183.2	c.*225C>T		3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD11	ENST00000301030.10	c.*225C>T		3_prime_UTR_variant	13/13	5	NM_013275.6	P1
	ENST00000602042.1	n.150G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 47 AN: 76896 Hom.: 0 Cov.: 9 FAILED QC

Gnomad AFR AF: 0.000111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00531

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000525

Gnomad FIN AF: 0.000777

Gnomad MID AF: 0.0116

Gnomad NFE AF: 0.000662

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000700 AC: 33 AN: 47132 Hom.: 0 AF XY: 0.000621 AC XY: 15 AN XY: 24142

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000126

Gnomad ASJ exome AF: 0.00633

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000577

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000965

Gnomad OTH exome AF: 0.00184

GnomAD4 exome AF: 0.000981 AC: 215 AN: 219238 Hom.: 2 Cov.: 0 AF XY: 0.00107 AC XY: 125 AN XY: 116690

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000987

Gnomad4 ASJ exome AF: 0.00728

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00122

Gnomad4 FIN exome AF: 0.00105

Gnomad4 NFE exome AF: 0.000773

Gnomad4 OTH exome AF: 0.00111

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000611 AC: 47 AN: 76924 Hom.: 0 Cov.: 9 AF XY: 0.000436 AC XY: 14 AN XY: 32094

Gnomad4 AFR AF: 0.000111

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00531

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000527

Gnomad4 FIN AF: 0.000777

Gnomad4 NFE AF: 0.000662

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00104 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 31, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	5.2
Dann	Benign	0.95

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: rs1235547589; hg19: chr16-89334661;