Variant chr18-36297724-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001281740.3(FHOD3):c.-112T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 756,258 control chromosomes in the GnomAD database, including 303,252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.90 ( 60152 hom., cov: 28)

Exomes 𝑓: 0.89 ( 243100 hom. )

Consequence

FHOD3
NM_001281740.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.595

Variant links:

Genes affected

FHOD3 (HGNC:26178): (formin homology 2 domain containing 3) The protein encoded by this gene is a member of the diaphanous-related formins (DRF), and contains multiple domains, including GBD (GTPase-binding domain), DID (diaphanous inhibitory domain), FH1 (formin homology 1), FH2 (formin homology 2), and DAD (diaphanous auto-regulatory domain) domains. This protein is thought to play a role in actin filament polymerization in cardiomyocytes. Mutations in this gene have been associated with dilated cardiomyopathy (DCM), characterized by dilation of the ventricular chamber, leading to impairment of systolic pump function and subsequent heart failure. Increased levels of the protein encoded by this gene have been observed in individuals with hypertrophic cardiomyopathy (HCM). Alternative splicing results in multiple transcript variants encoding different isoforms. A muscle-specific isoform has been shown to possess a casein kinase 2 (CK2) phosphorylation site at the C-terminal end of the FH2 domain. Phosphorylation of this site alters its interaction with sequestosome 1 (SQSTM1), and targets this isoform to myofibrils, while other isoforms form cytoplasmic aggregates. [provided by RefSeq, Aug 2015]

FHOD3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 18-36297724-T-C is Benign according to our data. Variant chr18-36297724-T-C is described in ClinVar as [Benign]. Clinvar id is 1221085.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FHOD3	NM_001281740.3 linkuse as main transcript	c.-112T>C		5_prime_UTR_variant	1/29	ENST00000590592.6

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FHOD3	ENST00000590592.6 linkuse as main transcript	c.-112T>C	5_prime_UTR_variant	1/29	1	NM_001281740.3	A2	Q2V2M9-4
FHOD3	ENST00000257209.8 linkuse as main transcript	c.-112T>C	5_prime_UTR_variant	1/25	1		P4	Q2V2M9-3
FHOD3	ENST00000589114.5 linkuse as main transcript	n.8T>C	non_coding_transcript_exon_variant	1/14	2

Frequencies

GnomAD3 genomes

AF:

0.902

AC:

132979

AN:

147390

Hom.:

60098

Cov.:

show subpopulations

Gnomad AFR

AF:

0.928

Gnomad AMI

AF:

0.942

Gnomad AMR

AF:

0.906

Gnomad ASJ

AF:

0.771

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.803

Gnomad FIN

AF:

0.910

Gnomad MID

AF:

0.795

Gnomad NFE

AF:

0.892

Gnomad OTH

AF:

0.879

GnomAD4 exome

AF:

0.893

AC:

543542

AN:

608764

Hom.:

243100

Cov.:

AF XY:

0.892

AC XY:

260369

AN XY:

291964

show subpopulations

Gnomad4 AFR exome

AF:

0.929

Gnomad4 AMR exome

AF:

0.901

Gnomad4 ASJ exome

AF:

0.773

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.776

Gnomad4 FIN exome

AF:

0.895

Gnomad4 NFE exome

AF:

0.895

Gnomad4 OTH exome

AF:

0.879

GnomAD4 genome

AF:

0.902

AC:

133085

AN:

147494

Hom.:

60152

Cov.:

AF XY:

0.902

AC XY:

64882

AN XY:

71912

show subpopulations

Gnomad4 AFR

AF:

0.928

Gnomad4 AMR

AF:

0.906

Gnomad4 ASJ

AF:

0.771

Gnomad4 EAS

AF:

0.997

Gnomad4 SAS

AF:

0.804

Gnomad4 FIN

AF:

0.910

Gnomad4 NFE

AF:

0.892

Gnomad4 OTH

AF:

0.879

Alfa

AF:

0.884

Hom.:

2700

Bravo

AF:

0.906

Asia WGS

AF:

0.909

AC:

2895

AN:

3188

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over