Genetic Variant NM_014391.3:c.*570_*574delTTTTT (chr10-90912291-TAAAAA-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.*570_*574delTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0652 in 230 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 0.091 ( 214 hom., cov: 0)

Exomes 𝑓: 0.065 ( 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.570_574delTTTTT		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.570_574delTTTTT	3_prime_UTR	Exon 9 of 9	ENSP00000360762.3	Q15327
ANKRD1	ENST00000869698.1		c.570_574delTTTTT	3_prime_UTR	Exon 8 of 8	ENSP00000539757.1
ANKRD1	ENST00000945870.1		c.570_574delTTTTT	3_prime_UTR	Exon 8 of 8	ENSP00000615929.1

Frequencies

GnomAD3 genomes

AF:

0.0908

AC:

6379

AN:

70252

Hom.:

213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0710

Gnomad AMI

AF:

0.0381

Gnomad AMR

AF:

0.0865

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.00209

Gnomad SAS

AF:

0.0480

Gnomad FIN

AF:

0.0524

Gnomad MID

AF:

0.125

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.0803

GnomAD4 exome

AF:

0.0652

AC:

AN:

230

Hom.:

AF XY:

0.0288

AC XY:

AN XY:

104

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:

0.0833

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0833

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0625

AC:

AN:

160

Other (OTH)

AF:

0.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000174544), 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:

0.0908

AC:

6380

AN:

70266

Hom.:

214

Cov.:

AF XY:

0.0881

AC XY:

2783

AN XY:

31598

show subpopulations

African (AFR)

AF:

0.0709

AC:

1529

AN:

21562

American (AMR)

AF:

0.0869

AC:

456

AN:

5246

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

200

AN:

1988

East Asian (EAS)

AF:

0.00210

AC:

AN:

2380

South Asian (SAS)

AF:

0.0475

AC:

AN:

1622

European-Finnish (FIN)

AF:

0.0524

AC:

AN:

916

Middle Eastern (MID)

AF:

0.125

AC:

AN:

European-Non Finnish (NFE)

AF:

0.113

AC:

3961

AN:

35004

Other (OTH)

AF:

0.0805

AC:

AN:

882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

225

450

675

900

1125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<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

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NM_014391.3:c.570_574delTTTTT

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