chr10-90918981-A-AAAATAAAT

Variant names:

• chr10-90918981-A-AAAATAAAT
• rs397517250
• NM_014391.3:c.346-17_346-10dupATTTATTT

Variant summary

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

The NM_014391.3(ANKRD1):​c.346-17_346-10dupATTTATTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 91,028 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000011 (0 hom., cov: 18)
• Consequence: ANKRD1 NM_014391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181
• Publications: 3 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.346-17_346-10dupATTTATTT		intron	N/A	NP_055206.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD1	ENST00000371697.4	TSL:1 MANE Select	c.346-10_346-9insATTTATTT		intron	N/A	ENSP00000360762.3	Q15327
	ANKRD1	ENST00000869698.1		c.346-10_346-9insATTTATTT		intron	N/A	ENSP00000539757.1
	ANKRD1	ENST00000945870.1		c.346-10_346-9insATTTATTT		intron	N/A	ENSP00000615929.1

Frequencies

GnomAD3 genomes AF: 0.0000110 AC: 1 AN: 91028 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.0000368

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 26

GnomAD4 genome AF: 0.0000110 AC: 1 AN: 91028 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 43534

African (AFR) AF: 0.0000368 AC: 1 AN: 27142

American (AMR) AF: 0.00 AC: 0 AN: 8878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2240

East Asian (EAS) AF: 0.00 AC: 0 AN: 3488

South Asian (SAS) AF: 0.00 AC: 0 AN: 2892

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 224

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 39976

Other (OTH) AF: 0.00 AC: 0 AN: 1274

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs397517250; hg19: chr10-92678738;