Genetic Variant FAM53C:p.Arg129Cys (chr5-138345073-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016605.3(FAM53C):c.385C>T(p.Arg129Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000725 in 1,613,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

FAM53C
NM_016605.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.581

Variant links:

Genes affected

FAM53C (HGNC:1336): (family with sequence similarity 53 member C) The protein encoded by this gene belongs to the FAM53 protein family. FAM53 protein family members bind to a transcriptional regulator that modulates cell proliferation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

FAM53C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2613452).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM53C	NM_016605.3 link	c.385C>T	p.Arg129Cys	missense_variant	Exon 4 of 5	ENST00000239906.10	NP_057689.1	Q9NYF3
FAM53C	NM_001135647.2 link	c.385C>T	p.Arg129Cys	missense_variant	Exon 4 of 5		NP_001129119.1	Q9NYF3
FAM53C	NM_001350195.2 link	c.355C>T	p.Arg119Cys	missense_variant	Exon 4 of 5		NP_001337124.1
FAM53C	NM_001350194.2 link	c.137-385C>T		intron_variant	Intron 3 of 4		NP_001337123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM53C	ENST00000239906.10 link	c.385C>T	p.Arg129Cys	missense_variant	Exon 4 of 5	1	NM_016605.3	ENSP00000239906.5		Q9NYF3

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000558

AC:

AN:

250908

Hom.:

AF XY:

0.0000664

AC XY:

AN XY:

135642

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000746

AC:

109

AN:

1461700

Hom.:

Cov.:

AF XY:

0.0000770

AC XY:

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000863

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000453

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.385C>T (p.R129C) alteration is located in exon 4 (coding exon 3) of the FAM53C gene. This alteration results from a C to T substitution at nucleotide position 385, causing the arginine (R) at amino acid position 129 to be replaced by a cysteine (C). 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

0.13

BayesDel_addAF

Uncertain

0.050

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.20

T;T;T

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.88

.;D;D

M_CAP

Benign

0.026

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.8

L;L;.

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Benign

0.26

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.022

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.67

MutPred

0.35

Gain of catalytic residue at W130 (P = 5e-04);Gain of catalytic residue at W130 (P = 5e-04);.;

MVP

0.26

MPC

0.46

ClinPred

0.44

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.46

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