Variant 5-72989496-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_138782.3(FCHO2):c.195A>C(p.Gln65His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000325 in 1,599,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

FCHO2
NM_138782.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.443

Variant links:

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]

FCHO2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022460759).

BS2

High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCHO2	NM_138782.3 linkuse as main transcript	c.195A>C	p.Gln65His	missense_variant	3/26	ENST00000430046.7	NP_620137.2	Q0JRZ9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FCHO2	ENST00000430046.7 linkuse as main transcript	c.195A>C	p.Gln65His	missense_variant	3/26	1	NM_138782.3	ENSP00000393776.2	Q0JRZ9-1
FCHO2	ENST00000287761.7 linkuse as main transcript	c.195A>C	p.Gln65His	missense_variant	3/11	1		ENSP00000287761.6	H7BXJ4
FCHO2	ENST00000512348.5 linkuse as main transcript	c.195A>C	p.Gln65His	missense_variant	3/25	2		ENSP00000427296.1	Q0JRZ9-3
FCHO2	ENST00000507345.6 linkuse as main transcript	c.126-982A>C		intron_variant		5		ENSP00000426842.2	H0YAE2

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000886

AC:

AN:

225834

Hom.:

AF XY:

0.000107

AC XY:

AN XY:

121244

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000956

Gnomad SAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000177

GnomAD4 exome

AF:

0.0000297

AC:

AN:

1447284

Hom.:

Cov.:

AF XY:

0.0000390

AC XY:

AN XY:

718240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000533

Gnomad4 SAS exome

AF:

0.000156

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000150

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.000124

AC:

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 10, 2024

The c.195A>C (p.Q65H) alteration is located in exon 3 (coding exon 3) of the FCHO2 gene. This alteration results from a A to C substitution at nucleotide position 195, causing the glutamine (Q) at amino acid position 65 to be replaced by a histidine (H). 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

Benign

0.27

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0035

T;.;T

Eigen

Benign

-0.055

Eigen_PC

Benign

-0.024

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.81

T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.022

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;M;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.7

N;N;D

REVEL

Benign

0.13

Sift

Benign

0.24

T;T;T

Sift4G

Benign

0.14

T;T;T

Polyphen

1.0

D;.;.

Vest4

0.39

MutPred

0.50

Loss of MoRF binding (P = 0.1036);Loss of MoRF binding (P = 0.1036);Loss of MoRF binding (P = 0.1036);

MVP

0.52

MPC

0.28

ClinPred

0.087

GERP RS

2.7

Varity_R

0.49

gMVP

0.56

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

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