NM_013275.6:c.3822C>T

Variant names:

• chr16-89282720-G-A
• rs61741725
• NM_013275.6:c.3822C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_013275.6(ANKRD11):​c.3822C>T​(p.Ala1274Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 1,613,692 control chromosomes in the GnomAD database, including 1,594 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (150 hom., cov: 32)
  • Exomes 𝑓: 0.040 (1444 hom.)
• Consequence: ANKRD11 NM_013275.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -4.71
• Publications: 6 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: Ambry Genetics, G2P, Illumina, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen
• congenital heart defects, multiple types

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-89282720-G-A is Benign according to our data. Variant chr16-89282720-G-A is described in ClinVar as Benign. ClinVar VariationId is 380366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.71 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0581 is higher than 0.05.

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.3822C>T	p.Ala1274Ala	synonymous	Exon 9 of 13	NP_037407.4
	ANKRD11	NM_001256182.2		c.3822C>T	p.Ala1274Ala	synonymous	Exon 10 of 14	NP_001243111.1	Q6UB99
	ANKRD11	NM_001256183.2		c.3822C>T	p.Ala1274Ala	synonymous	Exon 9 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.3822C>T	p.Ala1274Ala	synonymous	Exon 9 of 13	ENSP00000301030.4	Q6UB99
	ANKRD11	ENST00000378330.7	TSL:1	c.3822C>T	p.Ala1274Ala	synonymous	Exon 10 of 14	ENSP00000367581.2	Q6UB99
	ANKRD11	ENST00000642600.2		c.3822C>T	p.Ala1274Ala	synonymous	Exon 9 of 13	ENSP00000495226.1	Q6UB99

Frequencies

GnomAD3 genomes AF: 0.0337 AC: 5116 AN: 151870 Hom.: 150 Cov.: 32

Gnomad AFR AF: 0.00733

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0245

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.0634

Gnomad SAS AF: 0.0154

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0380

Gnomad OTH AF: 0.0254

GnomAD2 exomes AF: 0.0400 AC: 10054 AN: 251352 AF XY: 0.0392

Gnomad AFR exome AF: 0.00739

Gnomad AMR exome AF: 0.0285

Gnomad ASJ exome AF: 0.0103

Gnomad EAS exome AF: 0.0664

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.0382

Gnomad OTH exome AF: 0.0427

GnomAD4 exome AF: 0.0396 AC: 57821 AN: 1461704 Hom.: 1444 Cov.: 37 AF XY: 0.0385 AC XY: 28025 AN XY: 727164

African (AFR) AF: 0.00624 AC: 209 AN: 33480

American (AMR) AF: 0.0292 AC: 1308 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0113 AC: 295 AN: 26136

East Asian (EAS) AF: 0.0624 AC: 2479 AN: 39700

South Asian (SAS) AF: 0.0115 AC: 996 AN: 86254

European-Finnish (FIN) AF: 0.122 AC: 6470 AN: 53244

Middle Eastern (MID) AF: 0.00729 AC: 42 AN: 5764

European-Non Finnish (NFE) AF: 0.0395 AC: 43904 AN: 1112008

Other (OTH) AF: 0.0351 AC: 2118 AN: 60394

GnomAD4 genome AF: 0.0337 AC: 5117 AN: 151988 Hom.: 150 Cov.: 32 AF XY: 0.0374 AC XY: 2781 AN XY: 74280

African (AFR) AF: 0.00731 AC: 303 AN: 41438

American (AMR) AF: 0.0244 AC: 373 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00980 AC: 34 AN: 3468

East Asian (EAS) AF: 0.0637 AC: 329 AN: 5162

South Asian (SAS) AF: 0.0156 AC: 75 AN: 4812

European-Finnish (FIN) AF: 0.129 AC: 1361 AN: 10528

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0381 AC: 2587 AN: 67988

Other (OTH) AF: 0.0251 AC: 53 AN: 2112

Alfa AF: 0.0281 Hom.: 57

Bravo AF: 0.0251

Asia WGS AF: 0.0400 AC: 140 AN: 3478

EpiCase AF: 0.0307

EpiControl AF: 0.0293

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	KBG syndrome (2)
-	-	2	not specified (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.053
DANN	Benign	0.40
PhyloP100		-4.7
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2
Mutation Taster		=94/6	polymorphism (auto)

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: rs61741725; hg19: chr16-89349128; COSMIC: COSV56357482; COSMIC: COSV56357482;