NM_013275.6:c.7977A>T

Variant names:

• chr16-89268493-T-A
• rs756775535
• NM_013275.6:c.7977A>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_013275.6(ANKRD11):​c.7977A>T​(p.Val2659Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 1,348,356 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000012 (1 hom.)
• Consequence: ANKRD11 NM_013275.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.984
• 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: Ambry Genetics, G2P, Illumina, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen
• congenital heart defects, multiple types

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000268218 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 16-89268493-T-A is Benign according to our data. Variant chr16-89268493-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2970088.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.984 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 15 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.7977A>T	p.Val2659Val	synonymous	Exon 13 of 13	NP_037407.4
	ANKRD11	NM_001256182.2		c.7977A>T	p.Val2659Val	synonymous	Exon 14 of 14	NP_001243111.1	Q6UB99
	ANKRD11	NM_001256183.2		c.7977A>T	p.Val2659Val	synonymous	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.7977A>T	p.Val2659Val	synonymous	Exon 13 of 13	ENSP00000301030.4	Q6UB99
	ANKRD11	ENST00000378330.7	TSL:1	c.7977A>T	p.Val2659Val	synonymous	Exon 14 of 14	ENSP00000367581.2	Q6UB99
	ANKRD11	ENST00000642600.2		c.7977A>T	p.Val2659Val	synonymous	Exon 13 of 13	ENSP00000495226.1	Q6UB99

Frequencies

GnomAD3 genomes AF: 0.0000142 AC: 2 AN: 140874 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000491

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000348 AC: 5 AN: 143578 AF XY: 0.0000518

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000124 AC: 15 AN: 1207370 Hom.: 1 Cov.: 17 AF XY: 0.0000133 AC XY: 8 AN XY: 601562

African (AFR) AF: 0.00 AC: 0 AN: 27868

American (AMR) AF: 0.00 AC: 0 AN: 35318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23842

East Asian (EAS) AF: 0.00 AC: 0 AN: 34700

South Asian (SAS) AF: 0.000187 AC: 14 AN: 74854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3714

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 909430

Other (OTH) AF: 0.0000194 AC: 1 AN: 51420

GnomAD4 genome AF: 0.0000142 AC: 2 AN: 140986 Hom.: 0 Cov.: 27 AF XY: 0.0000294 AC XY: 2 AN XY: 68096

African (AFR) AF: 0.00 AC: 0 AN: 37452

American (AMR) AF: 0.00 AC: 0 AN: 14040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3394

East Asian (EAS) AF: 0.00 AC: 0 AN: 4698

South Asian (SAS) AF: 0.000492 AC: 2 AN: 4064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9292

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64986

Other (OTH) AF: 0.00 AC: 0 AN: 1900

Alfa AF: 0.0000936 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	KBG syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		0.98

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: rs756775535; hg19: chr16-89334901;