Variant chr18-36298120-C-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.165+120C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 875,096 control chromosomes in the GnomAD database, including 59,418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.30 ( 8160 hom., cov: 31)

Exomes 𝑓: 0.36 ( 51258 hom. )

Consequence

FHOD3
NM_001281740.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.40

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=-0.8).

BP6

Variant 18-36298120-C-T is Benign according to our data. Variant chr18-36298120-C-T is described in ClinVar as [Benign]. Clinvar id is 1233999.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.394 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.165+120C>T		intron_variant		ENST00000590592.6

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
FHOD3	ENST00000590592.6 linkuse as main transcript	c.165+120C>T	intron_variant	1	NM_001281740.3	A2	Q2V2M9-4
FHOD3	ENST00000257209.8 linkuse as main transcript	c.165+120C>T	intron_variant	1		P4	Q2V2M9-3
FHOD3	ENST00000359247.8 linkuse as main transcript	c.165+120C>T	intron_variant	1		A2	Q2V2M9-1
FHOD3	ENST00000589114.5 linkuse as main transcript	n.284+120C>T	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.305

AC:

46181

AN:

151518

Hom.:

8156

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.492

Gnomad AMR

AF:

0.279

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.00275

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.452

Gnomad MID

AF:

0.226

Gnomad NFE

AF:

0.398

Gnomad OTH

AF:

0.288

GnomAD4 exome

AF:

0.357

AC:

258033

AN:

723470

Hom.:

51258

AF XY:

0.350

AC XY:

126459

AN XY:

361260

show subpopulations

Gnomad4 AFR exome

AF:

0.168

Gnomad4 AMR exome

AF:

0.292

Gnomad4 ASJ exome

AF:

0.236

Gnomad4 EAS exome

AF:

0.000657

Gnomad4 SAS exome

AF:

0.136

Gnomad4 FIN exome

AF:

0.452

Gnomad4 NFE exome

AF:

0.393

Gnomad4 OTH exome

AF:

0.318

GnomAD4 genome

AF:

0.305

AC:

46216

AN:

151626

Hom.:

8160

Cov.:

AF XY:

0.299

AC XY:

22127

AN XY:

74056

show subpopulations

Gnomad4 AFR

AF:

0.186

Gnomad4 AMR

AF:

0.279

Gnomad4 ASJ

AF:

0.237

Gnomad4 EAS

AF:

0.00275

Gnomad4 SAS

AF:

0.124

Gnomad4 FIN

AF:

0.452

Gnomad4 NFE

AF:

0.398

Gnomad4 OTH

AF:

0.285

Alfa

AF:

0.359

Hom.:

1768

Bravo

AF:

0.290

Asia WGS

AF:

0.0770

AC:

270

AN:

3462

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

Nov 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.73

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