rs1392970042

Variant names:

• chr16-89268210-C-T
• rs1392970042
• NM_013275.6:c.*268G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

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
• Publications: 0 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: Likely_benign. The variant received -6 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 VariationId is 1276986.Status of the report is criteria_provided_single_submitter, 1 stars.

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.*268G>A		3_prime_UTR	Exon 13 of 13	NP_037407.4
	ANKRD11	NM_001256182.2		c.*268G>A		3_prime_UTR	Exon 14 of 14	NP_001243111.1	Q6UB99
	ANKRD11	NM_001256183.2		c.*268G>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.*268G>A		3_prime_UTR	Exon 13 of 13	ENSP00000301030.4	Q6UB99
	ANKRD11	ENST00000378330.7	TSL:1	c.*268G>A		3_prime_UTR	Exon 14 of 14	ENSP00000367581.2	Q6UB99
	ANKRD11	ENST00000642600.2		c.*268G>A		3_prime_UTR	Exon 13 of 13	ENSP00000495226.1	Q6UB99

Frequencies

GnomAD3 genomes AF: 0.00316 AC: 286 AN: 90620 Hom.: 0 Cov.: 11

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

GnomAD2 exomes AF: 0.00364 AC: 128 AN: 35200 AF XY: 0.00375

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 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

African (AFR) AF: 0.000628 AC: 3 AN: 4780

American (AMR) AF: 0.00345 AC: 22 AN: 6372

Ashkenazi Jewish (ASJ) AF: 0.00705 AC: 27 AN: 3828

East Asian (EAS) AF: 0.00 AC: 0 AN: 6588

South Asian (SAS) AF: 0.00373 AC: 84 AN: 22490

European-Finnish (FIN) AF: 0.000304 AC: 2 AN: 6578

Middle Eastern (MID) AF: 0.0134 AC: 8 AN: 596

European-Non Finnish (NFE) AF: 0.00491 AC: 416 AN: 84780

Other (OTH) AF: 0.00295 AC: 23 AN: 7800

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

African (AFR) AF: 0.000734 AC: 16 AN: 21804

American (AMR) AF: 0.00310 AC: 25 AN: 8066

Ashkenazi Jewish (ASJ) AF: 0.00389 AC: 10 AN: 2568

East Asian (EAS) AF: 0.00 AC: 0 AN: 3342

South Asian (SAS) AF: 0.00136 AC: 3 AN: 2206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4844

Middle Eastern (MID) AF: 0.00407 AC: 1 AN: 246

European-Non Finnish (NFE) AF: 0.00491 AC: 225 AN: 45818

Other (OTH) AF: 0.00255 AC: 3 AN: 1178

Alfa AF: 0.00288 Hom.: 1

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	-0.53
CADD	Benign	1.6
DANN	Benign	0.88
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism

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: rs1392970042; hg19: chr16-89334618;