Variant 18-36355736-A-G 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.272+91A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 1,039,204 control chromosomes in the GnomAD database, including 1,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.014 ( 200 hom., cov: 32)

Exomes 𝑓: 0.015 ( 1206 hom. )

Consequence

FHOD3
NM_001281740.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.70

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=-0.84).

BP6

Variant 18-36355736-A-G is Benign according to our data. Variant chr18-36355736-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1317403.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.26 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.272+91A>G		intron_variant		ENST00000590592.6

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
FHOD3	ENST00000590592.6 linkuse as main transcript	c.272+91A>G	intron_variant	1	NM_001281740.3	A2	Q2V2M9-4
FHOD3	ENST00000257209.8 linkuse as main transcript	c.272+91A>G	intron_variant	1		P4	Q2V2M9-3
FHOD3	ENST00000359247.8 linkuse as main transcript	c.272+91A>G	intron_variant	1		A2	Q2V2M9-1
FHOD3	ENST00000589114.5 linkuse as main transcript	n.391+91A>G	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0141

AC:

2151

AN:

152150

Hom.:

200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00871

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.272

Gnomad SAS

AF:

0.0215

Gnomad FIN

AF:

0.00763

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00415

Gnomad OTH

AF:

0.0162

GnomAD4 exome

AF:

0.0146

AC:

12990

AN:

886936

Hom.:

1206

AF XY:

0.0147

AC XY:

6713

AN XY:

455648

show subpopulations

Gnomad4 AFR exome

AF:

0.00174

Gnomad4 AMR exome

AF:

0.00935

Gnomad4 ASJ exome

AF:

0.00537

Gnomad4 EAS exome

AF:

0.248

Gnomad4 SAS exome

AF:

0.0147

Gnomad4 FIN exome

AF:

0.00634

Gnomad4 NFE exome

AF:

0.00303

Gnomad4 OTH exome

AF:

0.0212

GnomAD4 genome

AF:

0.0141

AC:

2153

AN:

152268

Hom.:

200

Cov.:

AF XY:

0.0152

AC XY:

1129

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00221

Gnomad4 AMR

AF:

0.00876

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.272

Gnomad4 SAS

AF:

0.0224

Gnomad4 FIN

AF:

0.00763

Gnomad4 NFE

AF:

0.00415

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.00374

Hom.:

Bravo

AF:

0.0157

Asia WGS

AF:

0.120

AC:

416

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely 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

-0.84

CADD

Benign

0.99

DANN

Benign

0.69

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