10-90912291-TAAAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAA

Variant names:

• chr10-90912291-TAAAA-T
• rs71025330
• NM_014391.3:c.*571_*574delTTTT

Variant summary

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

The NM_014391.3(ANKRD1):​c.*571_*574delTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 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 0.022 (21 hom., cov: 0)
  • Exomes 𝑓: 0.021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD1 NM_014391.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• 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 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.*571_*574delTTTT		3_prime_UTR	Exon 9 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.*571_*574delTTTT		3_prime_UTR	Exon 9 of 9	ENSP00000360762.3	Q15327
	ANKRD1	ENST00000869698.1		c.*571_*574delTTTT		3_prime_UTR	Exon 8 of 8	ENSP00000539757.1
	ANKRD1	ENST00000945870.1		c.*571_*574delTTTT		3_prime_UTR	Exon 8 of 8	ENSP00000615929.1

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 1561 AN: 70328 Hom.: 21 Cov.: 0

Gnomad AFR AF: 0.0296

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00452

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0179

Gnomad FIN AF: 0.0393

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0222

Gnomad OTH AF: 0.0102

GnomAD4 exome AF: 0.0214 AC: 5 AN: 234 Hom.: 0 AF XY: 0.00943 AC XY: 1 AN XY: 106

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.0200 AC: 1 AN: 50

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AF: 0.00 AC: 0 AN: 14

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0250 AC: 4 AN: 160

Other (OTH) AF: 0.00 AC: 0 AN: 4

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0393885), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0222 AC: 1563 AN: 70342 Hom.: 21 Cov.: 0 AF XY: 0.0226 AC XY: 715 AN XY: 31610

African (AFR) AF: 0.0296 AC: 639 AN: 21578

American (AMR) AF: 0.0118 AC: 62 AN: 5268

Ashkenazi Jewish (ASJ) AF: 0.00452 AC: 9 AN: 1990

East Asian (EAS) AF: 0.00 AC: 0 AN: 2378

South Asian (SAS) AF: 0.0179 AC: 29 AN: 1616

European-Finnish (FIN) AF: 0.0393 AC: 36 AN: 916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 88

European-Non Finnish (NFE) AF: 0.0222 AC: 779 AN: 35046

Other (OTH) AF: 0.0102 AC: 9 AN: 882

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism

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: rs71025330; hg19: chr10-92672048;