Variant 16-67247319-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_013241.3(FHOD1):c.92G>A(p.Cys31Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000014 ( 0 hom. )

Consequence

FHOD1
NM_013241.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.55

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:

SLC9A5 (HGNC:11078): (solute carrier family 9 member A5) Predicted to enable potassium:proton antiporter activity and sodium:proton antiporter activity. Predicted to be involved in potassium ion transmembrane transport; regulation of intracellular pH; and sodium ion import across plasma membrane. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. Implicated in end stage renal disease. [provided by Alliance of Genome Resources, Apr 2022]

SLC9A5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39122427).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHOD1	NM_013241.3 link	c.92G>A	p.Cys31Tyr	missense_variant	1/22	ENST00000258201.9	NP_037373.2	Q9Y613

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHOD1	ENST00000258201.9 link	c.92G>A	p.Cys31Tyr	missense_variant	1/22	1	NM_013241.3	ENSP00000258201.4		Q9Y613

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461262

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726974

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

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:

152256

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Dec 03, 2024

The c.92G>A (p.C31Y) alteration is located in exon 1 (coding exon 1) of the FHOD1 gene. This alteration results from a G to A substitution at nucleotide position 92, causing the cysteine (C) at amino acid position 31 to be replaced by a tyrosine (Y). 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

Pathogenic

0.68

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

0.97

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.81

M_CAP

Benign

0.049

MetaRNN

Benign

0.39

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.14

Sift

Benign

0.13

Sift4G

Benign

0.18

Polyphen

0.97

Vest4

0.36

MutPred

0.45

Gain of phosphorylation at C31 (P = 0.0222);

MVP

0.69

MPC

2.2

ClinPred

0.96

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.39

gMVP

0.33

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