Variant chr16-67230125-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_013241.3(FHOD1):c.3155G>A(p.Ser1052Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,614,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

FHOD1
NM_013241.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0290

Variant links:

Genes affected

FHOD1 (HGNC:17905): (formin homology 2 domain containing 1) This gene encodes a protein which is a member of the formin/diaphanous family of proteins. The gene is ubiquitously expressed but is found in abundance in the spleen. The encoded protein has sequence homology to diaphanous and formin proteins within the Formin Homology (FH)1 and FH2 domains. It also contains a coiled-coil domain, a collagen-like domain, two nuclear localization signals, and several potential PKC and PKA phosphorylation sites. It is a predominantly cytoplasmic protein and is expressed in a variety of human cell lines. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

FHOD1 links:

FHOD1 (HGNC:):

FHOD1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024918467).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHOD1	NM_013241.3 linkuse as main transcript	c.3155G>A	p.Ser1052Asn	missense_variant	20/22	ENST00000258201.9	NP_037373.2	Q9Y613

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FHOD1	ENST00000258201.9 linkuse as main transcript	c.3155G>A	p.Ser1052Asn	missense_variant	20/22	1	NM_013241.3	ENSP00000258201.4	Q9Y613
FHOD1	ENST00000567752.5 linkuse as main transcript	n.3736G>A		non_coding_transcript_exon_variant	18/20	2
FHOD1	ENST00000569085.1 linkuse as main transcript	n.72G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251410

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000567

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

The c.3155G>A (p.S1052N) alteration is located in exon 20 (coding exon 20) of the FHOD1 gene. This alteration results from a G to A substitution at nucleotide position 3155, causing the serine (S) at amino acid position 1052 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.017

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.57

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.34

M_CAP

Benign

0.0046

MetaRNN

Benign

0.025

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.13

PrimateAI

Benign

0.35

PROVEAN

Benign

2.1

REVEL

Benign

0.080

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.15

MutPred

0.20

Loss of phosphorylation at S1052 (P = 0.0172);

MVP

0.29

MPC

0.19

ClinPred

0.033

GERP RS

1.0

Varity_R

0.075

gMVP

0.17

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