chr5-72990505-C-G

Variant names:

• chr5-72990505-C-G
• NM_138782.3:c.228C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138782.3(FCHO2):​c.228C>G​(p.Phe76Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FCHO2 NM_138782.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.952
• Publications: 0 publications found

Genes affected

FCHO2 (HGNC:25180): (FCH and mu domain containing endocytic adaptor 2) Enables identical protein binding activity. Involved in clathrin coat assembly and clathrin-dependent endocytosis. Located in clathrin-coated pit and clathrin-coated vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3094791).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138782.3. 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
	FCHO2	NM_138782.3	MANE Select	c.228C>G	p.Phe76Leu	missense	Exon 4 of 26	NP_620137.2	Q0JRZ9-1
	FCHO2	NM_001146032.2		c.228C>G	p.Phe76Leu	missense	Exon 4 of 25	NP_001139504.1	Q0JRZ9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCHO2	ENST00000430046.7	TSL:1 MANE Select	c.228C>G	p.Phe76Leu	missense	Exon 4 of 26	ENSP00000393776.2	Q0JRZ9-1
	FCHO2	ENST00000287761.7	TSL:1	c.228C>G	p.Phe76Leu	missense	Exon 4 of 11	ENSP00000287761.6	H7BXJ4
	FCHO2	ENST00000956652.1		c.228C>G	p.Phe76Leu	missense	Exon 4 of 27	ENSP00000626711.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

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	0.84
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-0.066
Eigen_PC	Benign	-0.0058
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.95
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.21
Sift	Benign	0.88	T
Sift4G	Benign	0.23	T
Polyphen		0.21	B
Vest4		0.74
MutPred		0.57		Gain of ubiquitination at K77 (P = 0.1504)
MVP		0.76
MPC		0.31
ClinPred		0.75	D
GERP RS		1.7
Varity_R		0.63
gMVP		0.52
Mutation Taster		=27/73	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr5-72286332;