Variant 5-73037178-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_138782.3(FCHO2):c.877C>T(p.Pro293Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00015 in 1,591,920 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

FCHO2
NM_138782.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.90

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:

FCHO2 (HGNC:):

FCHO2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08481482).

BS2

High AC in GnomAd4 at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCHO2	NM_138782.3 linkuse as main transcript	c.877C>T	p.Pro293Ser	missense_variant	10/26	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.877C>T	p.Pro293Ser	missense_variant	10/26	1	NM_138782.3	ENSP00000393776.2	Q0JRZ9-1
FCHO2	ENST00000287761.7 linkuse as main transcript	c.877C>T	p.Pro293Ser	missense_variant	10/11	1		ENSP00000287761.6	H7BXJ4
FCHO2	ENST00000512348.5 linkuse as main transcript	c.778C>T	p.Pro260Ser	missense_variant	9/25	2		ENSP00000427296.1	Q0JRZ9-3
FCHO2	ENST00000511264.1 linkuse as main transcript	n.270C>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

151716

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000324

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000105

AC:

AN:

237098

Hom.:

AF XY:

0.000101

AC XY:

AN XY:

128762

show subpopulations

Gnomad AFR exome

AF:

0.0000669

Gnomad AMR exome

AF:

0.0000630

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:

0.000202

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000147

AC:

211

AN:

1440204

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

105

AN XY:

716292

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000478

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:

0.000185

Gnomad4 OTH exome

AF:

0.0000842

GnomAD4 genome

AF:

0.000178

AC:

AN:

151716

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

74068

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000324

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000310

Hom.:

Bravo

AF:

0.000170

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000494

AC:

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

May 26, 2024

The c.877C>T (p.P293S) alteration is located in exon 10 (coding exon 10) of the FCHO2 gene. This alteration results from a C to T substitution at nucleotide position 877, causing the proline (P) at amino acid position 293 to be replaced by a serine (S). 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

0.082

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.066

T;.;T

Eigen

Benign

-0.054

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.085

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.94

L;.;.

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Benign

0.048

Sift

Benign

0.12

T;T;D

Sift4G

Benign

0.32

T;T;T

Polyphen

0.0030

B;.;.

Vest4

0.070

MVP

0.32

MPC

0.25

ClinPred

0.065

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.32

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over