10-90912291-TAAAAAAAAA-T

Variant names:

• chr10-90912291-TAAAAAAAAA-T
• rs71025330
• NM_014391.3:c.*566_*574delTTTTTTTTT

Variant summary

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

The NM_014391.3(ANKRD1):​c.*566_*574delTTTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0684 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.021 (30 hom., cov: 0)
  • Exomes 𝑓: 0.068 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD1 NM_014391.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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.*566_*574delTTTTTTTTT		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.*566_*574delTTTTTTTTT		3_prime_UTR	Exon 9 of 9	ENSP00000360762.3	Q15327
	ANKRD1	ENST00000869698.1		c.*566_*574delTTTTTTTTT		3_prime_UTR	Exon 8 of 8	ENSP00000539757.1
	ANKRD1	ENST00000945870.1		c.*566_*574delTTTTTTTTT		3_prime_UTR	Exon 8 of 8	ENSP00000615929.1

Frequencies

GnomAD3 genomes AF: 0.0207 AC: 1460 AN: 70388 Hom.: 30 Cov.: 0

Gnomad AFR AF: 0.00885

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.0220

Gnomad ASJ AF: 0.0296

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00617

Gnomad FIN AF: 0.0448

Gnomad MID AF: 0.0313

Gnomad NFE AF: 0.0259

Gnomad OTH AF: 0.0203

GnomAD4 exome AF: 0.0684 AC: 16 AN: 234 Hom.: 0 AF XY: 0.0660 AC XY: 7 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: 0.100 AC: 5 AN: 50

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

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

South Asian (SAS) AF: 0.0714 AC: 1 AN: 14

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

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0625 AC: 10 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 = 0.0000499621), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0207 AC: 1460 AN: 70402 Hom.: 30 Cov.: 0 AF XY: 0.0201 AC XY: 635 AN XY: 31630

African (AFR) AF: 0.00889 AC: 192 AN: 21598

American (AMR) AF: 0.0220 AC: 116 AN: 5272

Ashkenazi Jewish (ASJ) AF: 0.0296 AC: 59 AN: 1990

East Asian (EAS) AF: 0.00 AC: 0 AN: 2380

South Asian (SAS) AF: 0.00618 AC: 10 AN: 1618

European-Finnish (FIN) AF: 0.0448 AC: 41 AN: 916

Middle Eastern (MID) AF: 0.0227 AC: 2 AN: 88

European-Non Finnish (NFE) AF: 0.0259 AC: 907 AN: 35076

Other (OTH) AF: 0.0204 AC: 18 AN: 884

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Dilated Cardiomyopathy, Dominant (1)

Computational scores

Source: dbNSFP v4.9

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

Splicing

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

Other links and lift over

dbSNP: rs71025330; hg19: chr10-92672048;