rs397517250

Variant names:

• chr10-90918981-AAAATAAATAAAT-A
• rs397517250
• NM_014391.3:c.346-21_346-10delATTTATTTATTT

Your query was ambiguous. Multiple possible variants found:

• chr10-90918981-AAAATAAATAAAT-A
• chr10-90918981-AAAATAAATAAAT-AAAAT
• chr10-90918981-AAAATAAATAAAT-AAAATAAAT
• chr10-90918981-AAAATAAATAAAT-AAAATAAATAAATAAAT
• chr10-90918981-AAAATAAATAAAT-AAAATAAATAAATAAATAAAT

Variant summary

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

The NM_014391.3(ANKRD1):​c.346-21_346-10delATTTATTTATTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000164 in 1,221,750 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: ANKRD1 NM_014391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19
• Publications: 0 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
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD1	NM_014391.3	c.346-21_346-10delATTTATTTATTT		intron_variant	Intron 3 of 8	ENST00000371697.4	NP_055206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD1	ENST00000371697.4	c.346-21_346-10delATTTATTTATTT		intron_variant	Intron 3 of 8	1	NM_014391.3	ENSP00000360762.3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000164 AC: 2 AN: 1221750 Hom.: 0 AF XY: 0.00000325 AC XY: 2 AN XY: 614734

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

African (AFR) AF: 0.0000533 AC: 1 AN: 18760

American (AMR) AF: 0.00 AC: 0 AN: 39776

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23594

East Asian (EAS) AF: 0.00 AC: 0 AN: 30678

South Asian (SAS) AF: 0.00 AC: 0 AN: 73064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45242

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4832

European-Non Finnish (NFE) AF: 0.00000107 AC: 1 AN: 935466

Other (OTH) AF: 0.00 AC: 0 AN: 50338

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2

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;