16-67247304-T-C

Variant names:

• chr16-67247304-T-C
• NM_013241.3:c.107A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_013241.3(FHOD1):​c.107A>G​(p.Glu36Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,066 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FHOD1 NM_013241.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.83
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013241.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHOD1	NM_013241.3	MANE Select	c.107A>G	p.Glu36Gly	missense	Exon 1 of 22	NP_037373.2	Q9Y613
	FHOD1	NM_001318202.2		c.107A>G	p.Glu36Gly	missense	Exon 1 of 24	NP_001305131.1	A0A068F7M9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHOD1	ENST00000258201.9	TSL:1 MANE Select	c.107A>G	p.Glu36Gly	missense	Exon 1 of 22	ENSP00000258201.4	Q9Y613
	SLC9A5	ENST00000564704.5	TSL:1	n.775-5238T>C		intron	N/A
	FHOD1	ENST00000932114.1		c.107A>G	p.Glu36Gly	missense	Exon 1 of 24	ENSP00000602173.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461066 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726886

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111766

Other (OTH) AF: 0.00 AC: 0 AN: 60362

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		4.8
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.60
MutPred		0.26		Loss of disorder (P = 0.1322)
MVP		0.72
MPC		1.8
ClinPred		1.0	D
GERP RS		5.6
PromoterAI		0.055	Neutral
Varity_R		0.63
gMVP		0.63
Mutation Taster		=28/72	disease causing

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

Other links and lift over

hg19: chr16-67281207;