Variant 18-36297750-G-T 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.-86G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0853 in 1,127,724 control chromosomes in the GnomAD database, including 4,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.097 ( 752 hom., cov: 32)

Exomes 𝑓: 0.083 ( 3685 hom. )

Consequence

FHOD3
NM_001281740.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.195

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=-0.56).

BP6

Variant 18-36297750-G-T is Benign according to our data. Variant chr18-36297750-G-T is described in ClinVar as [Benign]. Clinvar id is 1287000.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.154 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.-86G>T		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.-86G>T	5_prime_UTR_variant	1/29	1	NM_001281740.3	A2	Q2V2M9-4
FHOD3	ENST00000257209.8 linkuse as main transcript	c.-86G>T	5_prime_UTR_variant	1/25	1		P4	Q2V2M9-3
FHOD3	ENST00000589114.5 linkuse as main transcript	n.34G>T	non_coding_transcript_exon_variant	1/14	2

Frequencies

GnomAD3 genomes

AF:

0.0972

AC:

14530

AN:

149538

Hom.:

752

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.0917

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.0718

Gnomad FIN

AF:

0.0676

Gnomad MID

AF:

0.115

Gnomad NFE

AF:

0.0823

Gnomad OTH

AF:

0.0979

GnomAD4 exome

AF:

0.0835

AC:

81652

AN:

978080

Hom.:

3685

Cov.:

AF XY:

0.0838

AC XY:

39653

AN XY:

473074

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.190

Gnomad4 ASJ exome

AF:

0.0952

Gnomad4 EAS exome

AF:

0.170

Gnomad4 SAS exome

AF:

0.0832

Gnomad4 FIN exome

AF:

0.0677

Gnomad4 NFE exome

AF:

0.0793

Gnomad4 OTH exome

AF:

0.0991

GnomAD4 genome

AF:

0.0971

AC:

14533

AN:

149644

Hom.:

752

Cov.:

AF XY:

0.0986

AC XY:

7207

AN XY:

73084

show subpopulations

Gnomad4 AFR

AF:

0.101

Gnomad4 AMR

AF:

0.159

Gnomad4 ASJ

AF:

0.0917

Gnomad4 EAS

AF:

0.157

Gnomad4 SAS

AF:

0.0714

Gnomad4 FIN

AF:

0.0676

Gnomad4 NFE

AF:

0.0823

Gnomad4 OTH

AF:

0.0988

Alfa

AF:

0.0918

Hom.:

Bravo

AF:

0.105

Asia WGS

AF:

0.123

AC:

417

AN:

3406

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

Feb 23, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.90

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