Genetic Variant ANKRD1:c.*569_*574delTTTTTT (chr10-90912291-TAAAAAA-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_014391.3(ANKRD1):c.*569_*574delTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0641 in 234 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.063 ( 213 hom., cov: 0)

Exomes 𝑓: 0.064 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANKRD1
NM_014391.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.63

Publications

1 publications found

Variant links:

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

ANKRD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.569_574delTTTTTT		3_prime_UTR	Exon 9 of 9	NP_055206.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANKRD1	ENST00000371697.4	TSL:1 MANE Select	c.569_574delTTTTTT	3_prime_UTR	Exon 9 of 9	ENSP00000360762.3	Q15327
ANKRD1	ENST00000869698.1		c.569_574delTTTTTT	3_prime_UTR	Exon 8 of 8	ENSP00000539757.1
ANKRD1	ENST00000945870.1		c.569_574delTTTTTT	3_prime_UTR	Exon 8 of 8	ENSP00000615929.1

Frequencies

GnomAD3 genomes

AF:

0.0633

AC:

4458

AN:

70392

Hom.:

213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0399

Gnomad ASJ

AF:

0.0241

Gnomad EAS

AF:

0.0770

Gnomad SAS

AF:

0.0419

Gnomad FIN

AF:

0.0871

Gnomad MID

AF:

0.0313

Gnomad NFE

AF:

0.0294

Gnomad OTH

AF:

0.0566

GnomAD4 exome

AF:

0.0641

AC:

AN:

234

Hom.:

AF XY:

0.0472

AC XY:

AN XY:

106

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AF:

0.160

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.167

AC:

AN:

South Asian (SAS)

AF:

0.143

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0250

AC:

AN:

160

Other (OTH)

AF:

0.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000844135), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.395

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0633

AC:

4460

AN:

70404

Hom.:

213

Cov.:

AF XY:

0.0673

AC XY:

2129

AN XY:

31632

show subpopulations

African (AFR)

AF:

0.129

AC:

2784

AN:

21594

American (AMR)

AF:

0.0398

AC:

210

AN:

5270

Ashkenazi Jewish (ASJ)

AF:

0.0241

AC:

AN:

1990

East Asian (EAS)

AF:

0.0772

AC:

184

AN:

2382

South Asian (SAS)

AF:

0.0420

AC:

AN:

1618

European-Finnish (FIN)

AF:

0.0871

AC:

AN:

918

Middle Eastern (MID)

AF:

0.0341

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0294

AC:

1033

AN:

35082

Other (OTH)

AF:

0.0567

AC:

AN:

882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

162

324

485

647

809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.6

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

10-90912291-TAAAAAAAAAAAAAAAAAA-TAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over