Genetic Variant NM_013241.3:c.235G>C (chr16-67239421-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_013241.3(FHOD1):c.235G>C(p.Gly79Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FHOD1
NM_013241.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.08

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.838

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHOD1	NM_013241.3 link	c.235G>C	p.Gly79Arg	missense_variant	Exon 2 of 22	ENST00000258201.9	NP_037373.2	Q9Y613

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FHOD1	ENST00000258201.9 link	c.235G>C	p.Gly79Arg	missense_variant	Exon 2 of 22	1	NM_013241.3	ENSP00000258201.4	Q9Y613
SLC9A5	ENST00000564704.5 link	n.774+965C>G		intron_variant	Intron 1 of 15	1
FHOD1	ENST00000561922.1 link	n.235G>C		non_coding_transcript_exon_variant	Exon 2 of 13	2		ENSP00000458085.1	H3BVE7
FHOD1	ENST00000567752.5 link	n.289G>C		non_coding_transcript_exon_variant	Exon 2 of 20	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251338

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461808

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.38

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.014

MetaRNN

Pathogenic

0.84

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

3.1

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-6.4

REVEL

Benign

0.29

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.93

MutPred

0.55

Gain of solvent accessibility (P = 0.0171);

MVP

0.71

MPC

1.8

ClinPred

0.99

GERP RS

4.9

Varity_R

0.77

gMVP

0.59

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over