Variant 20-35286824-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_178468.6(FAM83C):c.1955A>G(p.Asn652Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000427 in 1,613,934 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00070 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00040 ( 1 hom. )

Consequence

FAM83C
NM_178468.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.20

Variant links:

Genes affected

FAM83C (HGNC:16121): (family with sequence similarity 83 member C) This gene encodes a member of the family with sequence similarity 83 protein family. The encoded protein may be involved in regulating MAPK signaling in cancer cells. [provided by RefSeq, Mar 2017]

FAM83C 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=0.0036581159).

BP6

Variant 20-35286824-T-C is Benign according to our data. Variant chr20-35286824-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2258386.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM83C	NM_178468.6 link	c.1955A>G	p.Asn652Ser	missense_variant	4/4	ENST00000374408.4	NP_848563.1	Q9BQN1
FAM83C	XM_047439892.1 link	c.1427A>G	p.Asn476Ser	missense_variant	4/4		XP_047295848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM83C	ENST00000374408.4 link	c.1955A>G	p.Asn652Ser	missense_variant	4/4	1	NM_178468.6	ENSP00000363529.3		Q9BQN1

Frequencies

GnomAD3 genomes

AF:

0.000698

AC:

106

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000846

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000581

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000471

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000565

AC:

142

AN:

251344

Hom.:

AF XY:

0.000552

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000761

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000537

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000399

AC:

583

AN:

1461846

Hom.:

Cov.:

AF XY:

0.000400

AC XY:

291

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00172

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000328

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.000697

AC:

106

AN:

152088

Hom.:

Cov.:

AF XY:

0.000699

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.000844

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000583

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000471

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000385

Hom.:

Bravo

AF:

0.000941

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000494

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000830

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.0020

DANN

Benign

0.35

DEOGEN2

Benign

0.0062

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0099

LIST_S2

Benign

0.53

M_CAP

Benign

0.0016

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.48

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.20

REVEL

Benign

0.012

Sift

Benign

0.56

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.051

MVP

0.11

MPC

0.14

ClinPred

0.010

GERP RS

-8.8

Varity_R

0.026

gMVP

0.074

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