10-90912291-T-TAAAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_014391.3(ANKRD1):c.*574_*575insTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.082 (654 hom., cov: 0)
  • Exomes 𝑓: 0.0085 (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: -1.12

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd at 654 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD1	NM_014391.3	c.*574_*575insTTTTT		3_prime_UTR_variant	9/9	ENST00000371697.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD1	ENST00000371697.4	c.*574_*575insTTTTT		3_prime_UTR_variant	9/9	1	NM_014391.3	P1

Frequencies

GnomAD3 genomes AF: 0.0817 AC: 5724 AN: 70070 Hom.: 654 Cov.: 0

Gnomad AFR AF: 0.0613

Gnomad AMI AF: 0.0909

Gnomad AMR AF: 0.0888

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0877

Gnomad SAS AF: 0.0667

Gnomad FIN AF: 0.0389

Gnomad MID AF: 0.0106

Gnomad NFE AF: 0.0919

Gnomad OTH AF: 0.0839

GnomAD4 exome AF: 0.00855 AC: 2 AN: 234 Hom.: 0 Cov.: 0 AF XY: 0.00943 AC XY: 1 AN XY: 106

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0125

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0817 AC: 5724 AN: 70080 Hom.: 654 Cov.: 0 AF XY: 0.0797 AC XY: 2510 AN XY: 31482

Gnomad4 AFR AF: 0.0612

Gnomad4 AMR AF: 0.0888

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.0875

Gnomad4 SAS AF: 0.0669

Gnomad4 FIN AF: 0.0389

Gnomad4 NFE AF: 0.0918

Gnomad4 OTH AF: 0.0841

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dilated Cardiomyopathy, Dominant Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71025330; hg19: chr10-92672048;