rs727502889

Variant names:

• chr10-90917826-T-A
• rs727502889
• NM_014391.3:c.458A>T
• ANKRD1 p.Lys153Ile

Your query was ambiguous. Multiple possible variants found:

• chr10-90917826-T-A
• chr10-90917826-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014391.3(ANKRD1):​c.458A>T​(p.Lys153Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,612,976 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ANKRD1 NM_014391.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 3.63
• Publications: 1 publications found

Genes affected

ANKRD1 (HGNC:15819): (ankyrin repeat domain 1) The protein encoded by this gene is localized to the nucleus of endothelial cells and is induced by IL-1 and TNF-alpha stimulation. Studies in rat cardiomyocytes suggest that this gene functions as a transcription factor. Interactions between this protein and the sarcomeric proteins myopalladin and titin suggest that it may also be involved in the myofibrillar stretch-sensor system. [provided by RefSeq, Jul 2008]

ANKRD1 Gene-Disease associations (from GenCC):

• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014391.3. 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
	ANKRD1	NM_014391.3	MANE Select	c.458A>T	p.Lys153Ile	missense	Exon 5 of 9	NP_055206.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD1	ENST00000371697.4	TSL:1 MANE Select	c.458A>T	p.Lys153Ile	missense	Exon 5 of 9	ENSP00000360762.3	Q15327
	ANKRD1	ENST00000945870.1		c.458A>T	p.Lys153Ile	missense	Exon 5 of 8	ENSP00000615929.1
	ANKRD1	ENST00000869699.1		c.320A>T	p.Lys107Ile	missense	Exon 4 of 8	ENSP00000539758.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152236 Hom.: 0 Cov.: 32

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460740 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726802

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111078

Other (OTH) AF: 0.00 AC: 0 AN: 60358

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74386

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Dilated Cardiomyopathy, Dominant (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		3.6
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.033	D
Varity_R		0.50
gMVP		0.67
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs727502889; hg19: chr10-92677583;