16-89268198-G-C

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.*280C>G 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0056 (1 hom., cov: 11)
  • Exomes 𝑓: 0.0069 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD11 NM_013275.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.18

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=-0.98).
• BP6: Variant 16-89268198-G-C is Benign according to our data. Variant chr16-89268198-G-C is described in ClinVar as [Benign]. Clinvar id is 1273107.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.00687 (644/93788) while in subpopulation NFE AF= 0.0097 (547/56378). AF 95% confidence interval is 0.00903. There are 2 homozygotes in gnomad4_exome. There are 293 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAdExome at 124 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD11	NM_013275.6	c.*280C>G		3_prime_UTR_variant	13/13	ENST00000301030.10
ANKRD11	NM_001256182.2	c.*280C>G		3_prime_UTR_variant	14/14
ANKRD11	NM_001256183.2	c.*280C>G		3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD11	ENST00000301030.10	c.*280C>G		3_prime_UTR_variant	13/13	5	NM_013275.6	P1
	ENST00000602042.1	n.95G>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 533 AN: 95530 Hom.: 1 Cov.: 11 FAILED QC

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00627

Gnomad AMR AF: 0.00642

Gnomad ASJ AF: 0.000375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00892

Gnomad MID AF: 0.00373

Gnomad NFE AF: 0.00804

Gnomad OTH AF: 0.00491

GnomAD3 exomes AF: 0.00516 AC: 124 AN: 24008 Hom.: 0 AF XY: 0.00457 AC XY: 58 AN XY: 12682

Gnomad AFR exome AF: 0.00130

Gnomad AMR exome AF: 0.00504

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00960

Gnomad OTH exome AF: 0.00569

GnomAD4 exome AF: 0.00687 AC: 644 AN: 93788 Hom.: 2 Cov.: 0 AF XY: 0.00592 AC XY: 293 AN XY: 49454

Gnomad4 AFR exome AF: 0.000933

Gnomad4 AMR exome AF: 0.00514

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000380

Gnomad4 FIN exome AF: 0.00885

Gnomad4 NFE exome AF: 0.00970

Gnomad4 OTH exome AF: 0.00592

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00557 AC: 533 AN: 95608 Hom.: 1 Cov.: 11 AF XY: 0.00549 AC XY: 229 AN XY: 41686

Gnomad4 AFR AF: 0.00146

Gnomad4 AMR AF: 0.00641

Gnomad4 ASJ AF: 0.000375

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00892

Gnomad4 NFE AF: 0.00804

Gnomad4 OTH AF: 0.00484

Alfa AF: 0.00432 Hom.: 3

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 04, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.66
Dann	Benign	0.49

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: rs1234224637; hg19: chr16-89334606;