16-89268210-C-T

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.*268G>A 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 0.0032 (0 hom., cov: 11)
  • Exomes 𝑓: 0.0041 (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: -0.375

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=-0.53).
• BP6: Variant 16-89268210-C-T is Benign according to our data. Variant chr16-89268210-C-T is described in ClinVar as [Benign]. Clinvar id is 1276986.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome at 128 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD11	NM_013275.6	c.*268G>A		3_prime_UTR_variant	13/13	ENST00000301030.10
ANKRD11	NM_001256182.2	c.*268G>A		3_prime_UTR_variant	14/14
ANKRD11	NM_001256183.2	c.*268G>A		3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD11	ENST00000301030.10	c.*268G>A		3_prime_UTR_variant	13/13	5	NM_013275.6	P1
	ENST00000602042.1	n.107C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 286 AN: 90620 Hom.: 0 Cov.: 11 FAILED QC

Gnomad AFR AF: 0.000737

Gnomad AMI AF: 0.00489

Gnomad AMR AF: 0.00310

Gnomad ASJ AF: 0.00389

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00136

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00373

Gnomad NFE AF: 0.00491

Gnomad OTH AF: 0.00258

GnomAD3 exomes AF: 0.00364 AC: 128 AN: 35200 Hom.: 1 AF XY: 0.00375 AC XY: 69 AN XY: 18390

Gnomad AFR exome AF: 0.000789

Gnomad AMR exome AF: 0.00363

Gnomad ASJ exome AF: 0.00668

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00343

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00542

Gnomad OTH exome AF: 0.00485

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00407 AC: 585 AN: 143812 Hom.: 4 Cov.: 0 AF XY: 0.00417 AC XY: 317 AN XY: 76078

Gnomad4 AFR exome AF: 0.000628

Gnomad4 AMR exome AF: 0.00345

Gnomad4 ASJ exome AF: 0.00705

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00373

Gnomad4 FIN exome AF: 0.000304

Gnomad4 NFE exome AF: 0.00491

Gnomad4 OTH exome AF: 0.00295

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00315 AC: 286 AN: 90686 Hom.: 0 Cov.: 11 AF XY: 0.00297 AC XY: 116 AN XY: 39118

Gnomad4 AFR AF: 0.000734

Gnomad4 AMR AF: 0.00310

Gnomad4 ASJ AF: 0.00389

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00136

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00491

Gnomad4 OTH AF: 0.00255

Alfa AF: 0.00288 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	-0.53
Cadd	Benign	1.6
Dann	Benign	0.88

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: rs1392970042; hg19: chr16-89334618;