Variant 3-112116742-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001171747.2(C3orf52):c.497T>C(p.Leu166Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000753 in 1,553,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

C3orf52
NM_001171747.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.152

Variant links:

Genes affected

C3orf52 (HGNC:26255): (chromosome 3 open reading frame 52) Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

C3orf52 links:

C3orf52 (HGNC:):

C3orf52 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=0.087002665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C3orf52	NM_024616.3 linkuse as main transcript	c.*96T>C		3_prime_UTR_variant	6/6	ENST00000264848.10	NP_078892.3	Q5BVD1-1
C3orf52	NM_001171747.2 linkuse as main transcript	c.497T>C	p.Leu166Ser	missense_variant	4/4		NP_001165218.1	Q5BVD1-3
C3orf52	XR_007095726.1 linkuse as main transcript	n.769T>C		non_coding_transcript_exon_variant	6/8
C3orf52	XR_924171.4 linkuse as main transcript	n.769T>C		non_coding_transcript_exon_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C3orf52	ENST00000264848.10 linkuse as main transcript	c.*96T>C		3_prime_UTR_variant	6/6	1	NM_024616.3	ENSP00000264848.5		Q5BVD1-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152190

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:

0.0000250

AC:

AN:

160226

Hom.:

AF XY:

0.0000237

AC XY:

AN XY:

84396

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:

0.00

Gnomad NFE exome

AF:

0.0000631

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000778

AC:

109

AN:

1401432

Hom.:

Cov.:

AF XY:

0.0000882

AC XY:

AN XY:

691536

show subpopulations

Gnomad4 AFR exome

AF:

0.0000314

Gnomad4 AMR exome

AF:

0.00

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:

0.0000963

Gnomad4 OTH exome

AF:

0.0000688

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74350

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:

0.0000712

Hom.:

Bravo

AF:

0.0000340

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

Aug 16, 2021

The c.497T>C (p.L166S) alteration is located in exon 4 (coding exon 4) of the C3orf52 gene. This alteration results from a T to C substitution at nucleotide position 497, causing the leucine (L) at amino acid position 166 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

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.50

CADD

Benign

5.2

DANN

Benign

0.66

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.045

M_CAP

Benign

0.0030

MetaRNN

Benign

0.087

MetaSVM

Benign

-1.1

PROVEAN

Benign

-0.48

REVEL

Benign

0.067

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.28

MutPred

0.29

Gain of disorder (P = 0.0064);

MVP

0.19

MPC

0.14

ClinPred

0.065

GERP RS

1.1

gMVP

0.15

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