16-67229861-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013241.3(FHOD1):​c.3344T>C​(p.Val1115Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

FHOD1
NM_013241.3 missense

Scores

2
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.02
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11766651).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FHOD1NM_013241.3 linkc.3344T>C p.Val1115Ala missense_variant 21/22 ENST00000258201.9 NP_037373.2 Q9Y613

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FHOD1ENST00000258201.9 linkc.3344T>C p.Val1115Ala missense_variant 21/221 NM_013241.3 ENSP00000258201.4 Q9Y613
FHOD1ENST00000567752.5 linkn.3925T>C non_coding_transcript_exon_variant 19/202
FHOD1ENST00000569085.1 linkn.261T>C non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsJun 09, 2022The c.3344T>C (p.V1115A) alteration is located in exon 21 (coding exon 21) of the FHOD1 gene. This alteration results from a T to C substitution at nucleotide position 3344, causing the valine (V) at amino acid position 1115 to be replaced by an alanine (A). 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
0.64
BayesDel_addAF
Benign
-0.0000052
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
22
DANN
Benign
0.87
DEOGEN2
Benign
0.021
T
Eigen
Benign
-0.17
Eigen_PC
Benign
0.071
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.72
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
0.95
N
REVEL
Benign
0.15
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.043
B
Vest4
0.38
MutPred
0.17
Loss of stability (P = 0.0209);
MVP
0.61
MPC
0.87
ClinPred
0.67
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.15
gMVP
0.41

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-67263764; API