16-89268213-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_013275.6(ANKRD11):c.*265C>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 0.0029 (0 hom., cov: 11)
  • Exomes 𝑓: 0.0039 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD11 NM_013275.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0470

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 16-89268213-G-C is Benign according to our data. Variant chr16-89268213-G-C is described in ClinVar as [Benign]. Clinvar id is 1222539.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome at 122 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD11	NM_013275.6	c.*265C>G		3_prime_UTR_variant	13/13	ENST00000301030.10
ANKRD11	NM_001256182.2	c.*265C>G		3_prime_UTR_variant	14/14
ANKRD11	NM_001256183.2	c.*265C>G		3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD11	ENST00000301030.10	c.*265C>G		3_prime_UTR_variant	13/13	5	NM_013275.6	P1
	ENST00000602042.1	n.110G>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 262 AN: 90026 Hom.: 0 Cov.: 11 FAILED QC

Gnomad AFR AF: 0.000836

Gnomad AMI AF: 0.00490

Gnomad AMR AF: 0.00298

Gnomad ASJ AF: 0.00392

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000918

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00376

Gnomad NFE AF: 0.00444

Gnomad OTH AF: 0.00172

GnomAD3 exomes AF: 0.00334 AC: 122 AN: 36534 Hom.: 1 AF XY: 0.00346 AC XY: 66 AN XY: 19092

Gnomad AFR exome AF: 0.000504

Gnomad AMR exome AF: 0.00346

Gnomad ASJ exome AF: 0.00640

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00355

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00488

Gnomad OTH exome AF: 0.00473

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00389 AC: 587 AN: 151024 Hom.: 4 Cov.: 0 AF XY: 0.00398 AC XY: 318 AN XY: 79968

Gnomad4 AFR exome AF: 0.000600

Gnomad4 AMR exome AF: 0.00328

Gnomad4 ASJ exome AF: 0.00648

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00403

Gnomad4 FIN exome AF: 0.000288

Gnomad4 NFE exome AF: 0.00456

Gnomad4 OTH exome AF: 0.00293

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00291 AC: 262 AN: 90086 Hom.: 0 Cov.: 11 AF XY: 0.00279 AC XY: 108 AN XY: 38740

Gnomad4 AFR AF: 0.000833

Gnomad4 AMR AF: 0.00298

Gnomad4 ASJ AF: 0.00392

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000920

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00444

Gnomad4 OTH AF: 0.00170

Alfa AF: 0.00282 Hom.: 1

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 13, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	4.0
Dann	Benign	0.71

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: rs1173080093; hg19: chr16-89334621;