NM_013275.6:c.*8G>A

Variant names:

• chr16-89268470-C-T
• rs553564829
• NM_013275.6:c.*8G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_013275.6(ANKRD11):​c.*8G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000373 in 1,205,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000081 (0 hom., cov: 24)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: ANKRD11 NM_013275.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.211
• Publications: 1 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: Orphanet, Illumina, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P
• congenital heart defects, multiple types

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000268218 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 16-89268470-C-T is Benign according to our data. Variant chr16-89268470-C-T is described in ClinVar as Benign. ClinVar VariationId is 2647056.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000809 (11/135960) while in subpopulation EAS AF = 0.00219 (10/4566). AF 95% confidence interval is 0.00119. There are 0 homozygotes in GnomAd4. There are 5 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High AC in GnomAd4 at 11 AD gene.

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.*8G>A		3_prime_UTR	Exon 13 of 13	NP_037407.4
	ANKRD11	NM_001256182.2		c.*8G>A		3_prime_UTR	Exon 14 of 14	NP_001243111.1	Q6UB99
	ANKRD11	NM_001256183.2		c.*8G>A		3_prime_UTR	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.*8G>A		3_prime_UTR	Exon 13 of 13	ENSP00000301030.4	Q6UB99
	ANKRD11	ENST00000378330.7	TSL:1	c.*8G>A		3_prime_UTR	Exon 14 of 14	ENSP00000367581.2	Q6UB99
	ANKRD11	ENST00000642600.2		c.*8G>A		3_prime_UTR	Exon 13 of 13	ENSP00000495226.1	Q6UB99

Frequencies

GnomAD3 genomes AF: 0.0000810 AC: 11 AN: 135858 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00218

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000157

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000979 AC: 13 AN: 132792 AF XY: 0.0000975

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00112

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000318 AC: 34 AN: 1069314 Hom.: 0 Cov.: 15 AF XY: 0.0000335 AC XY: 18 AN XY: 537146

African (AFR) AF: 0.00 AC: 0 AN: 25264

American (AMR) AF: 0.00 AC: 0 AN: 34910

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22516

East Asian (EAS) AF: 0.000766 AC: 26 AN: 33962

South Asian (SAS) AF: 0.0000282 AC: 2 AN: 70866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3488

European-Non Finnish (NFE) AF: 0.00000506 AC: 4 AN: 790396

Other (OTH) AF: 0.0000426 AC: 2 AN: 46902

GnomAD4 genome AF: 0.0000809 AC: 11 AN: 135960 Hom.: 0 Cov.: 24 AF XY: 0.0000767 AC XY: 5 AN XY: 65210

African (AFR) AF: 0.00 AC: 0 AN: 35606

American (AMR) AF: 0.00 AC: 0 AN: 13430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3352

East Asian (EAS) AF: 0.00219 AC: 10 AN: 4566

South Asian (SAS) AF: 0.00 AC: 0 AN: 3760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.0000157 AC: 1 AN: 63568

Other (OTH) AF: 0.00 AC: 0 AN: 1792

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000155

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.8
DANN	Benign	0.88
PhyloP100		0.21

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

Other links and lift over

dbSNP: rs553564829; hg19: chr16-89334878;