10-90912523-T-C

Position:

• chr10-90912523-T-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The NM_014391.3(ANKRD1):​c.*343A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 311,334 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0018 (1 hom.)
• Consequence: ANKRD1 NM_014391.3 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -0.0290

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-90912523-T-C is Benign according to our data. Variant chr10-90912523-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 301599.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD1	NM_014391.3	c.*343A>G		3_prime_UTR_variant	9/9	ENST00000371697.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD1	ENST00000371697.4	c.*343A>G		3_prime_UTR_variant	9/9	1	NM_014391.3	P1

Frequencies

GnomAD3 genomes AF: 0.00170 AC: 258 AN: 152130 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00223

Gnomad OTH AF: 0.00383

GnomAD4 exome AF: 0.00182 AC: 290 AN: 159086 Hom.: 1 Cov.: 0 AF XY: 0.00178 AC XY: 152 AN XY: 85576

Gnomad4 AFR exome AF: 0.000419

Gnomad4 AMR exome AF: 0.00109

Gnomad4 ASJ exome AF: 0.0165

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000430

Gnomad4 FIN exome AF: 0.000286

Gnomad4 NFE exome AF: 0.00196

Gnomad4 OTH exome AF: 0.00260

GnomAD4 genome AF: 0.00169 AC: 258 AN: 152248 Hom.: 0 Cov.: 31 AF XY: 0.00179 AC XY: 133 AN XY: 74434

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00223

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.000106 Hom.: 0

Bravo AF: 0.00189

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Primary dilated cardiomyopathy Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

ANKRD1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs41286920; hg19: chr10-92672280;