Variant 3-88156480-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173824.4(C3orf38):c.835A>G(p.Ser279Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000533 in 1,614,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

C3orf38
NM_173824.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.618

Variant links:

Genes affected

C3orf38 (HGNC:28384): (chromosome 3 open reading frame 38) Involved in positive regulation of apoptotic process. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

C3orf38 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.019029647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C3orf38	NM_173824.4 linkuse as main transcript	c.835A>G	p.Ser279Gly	missense_variant	3/3	ENST00000318887.8	NP_776185.2
C3orf38	XM_005264745.6 linkuse as main transcript	c.832A>G	p.Ser278Gly	missense_variant	3/3		XP_005264802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C3orf38	ENST00000318887.8 linkuse as main transcript	c.835A>G	p.Ser279Gly	missense_variant	3/3	1	NM_173824.4	ENSP00000322469	P1	Q5JPI3-1
C3orf38	ENST00000486971.1 linkuse as main transcript	c.*306A>G		3_prime_UTR_variant	3/3	2		ENSP00000418774

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000954

AC:

AN:

251470

Hom.:

AF XY:

0.0000883

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000472

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000402

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000112

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.000170

ExAC

AF:

0.0000741

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.835A>G (p.S279G) alteration is located in exon 3 (coding exon 3) of the C3orf38 gene. This alteration results from a A to G substitution at nucleotide position 835, causing the serine (S) at amino acid position 279 to be replaced by a glycine (G). 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

0.063

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.64

CADD

Benign

3.1

DANN

Benign

0.95

DEOGEN2

Benign

0.046

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.49

M_CAP

Benign

0.0042

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.97

MutationTaster

Benign

1.0

D;N

PROVEAN

Benign

-1.7

REVEL

Benign

0.045

Sift

Benign

0.19

Sift4G

Benign

0.22

Polyphen

0.0010

Vest4

0.042

MutPred

0.34

Loss of methylation at K274 (P = 0.0763);

MVP

0.10

MPC

0.15

ClinPred

0.039

GERP RS

-1.4

Varity_R

0.038

gMVP

0.25

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