Variant rs2291533 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001355236.2(C3orf49):c.759G>C(p.Gln253His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 702,790 control chromosomes in the GnomAD database, including 10,620 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 1872 hom., cov: 32)

Exomes 𝑓: 0.17 ( 8748 hom. )

Consequence

C3orf49
NM_001355236.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.310

Variant links:

Genes affected

C3orf49 (HGNC:25190): (chromosome 3 open reading frame 49)

C3orf49 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013246536).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
C3orf49	NM_001355236.2 linkuse as main transcript	c.759G>C	p.Gln253His	missense_variant	5/7	ENST00000295896.13
C3orf49	XM_024453353.2 linkuse as main transcript	c.759G>C	p.Gln253His	missense_variant	6/6
C3orf49	XM_047447470.1 linkuse as main transcript	c.555G>C	p.Gln185His	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
C3orf49	ENST00000295896.13 linkuse as main transcript	c.759G>C	p.Gln253His	missense_variant	5/7	2	NM_001355236.2	A2
C3orf49	ENST00000647022.1 linkuse as main transcript	c.759G>C	p.Gln253His	missense_variant	5/5			P2
C3orf49	ENST00000491896.1 linkuse as main transcript	c.384G>C	p.Gln128His	missense_variant	4/4	2
C3orf49	ENST00000673037.1 linkuse as main transcript	c.627G>C	p.Gln209His	missense_variant, splice_region_variant	4/5

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22869

AN:

152050

Hom.:

1873

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0785

Gnomad AMI

AF:

0.132

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.139

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.189

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.175

AC:

24528

AN:

139890

Hom.:

2272

AF XY:

0.175

AC XY:

13261

AN XY:

75720

show subpopulations

Gnomad AFR exome

AF:

0.0760

Gnomad AMR exome

AF:

0.216

Gnomad ASJ exome

AF:

0.196

Gnomad EAS exome

AF:

0.148

Gnomad SAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.141

Gnomad NFE exome

AF:

0.188

Gnomad OTH exome

AF:

0.172

GnomAD4 exome

AF:

0.174

AC:

95788

AN:

550622

Hom.:

8748

Cov.:

AF XY:

0.172

AC XY:

51380

AN XY:

298102

show subpopulations

Gnomad4 AFR exome

AF:

0.0784

Gnomad4 AMR exome

AF:

0.212

Gnomad4 ASJ exome

AF:

0.196

Gnomad4 EAS exome

AF:

0.131

Gnomad4 SAS exome

AF:

0.144

Gnomad4 FIN exome

AF:

0.142

Gnomad4 NFE exome

AF:

0.188

Gnomad4 OTH exome

AF:

0.169

GnomAD4 genome

AF:

0.150

AC:

22872

AN:

152168

Hom.:

1872

Cov.:

AF XY:

0.148

AC XY:

11034

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0784

Gnomad4 AMR

AF:

0.179

Gnomad4 ASJ

AF:

0.198

Gnomad4 EAS

AF:

0.139

Gnomad4 SAS

AF:

0.138

Gnomad4 FIN

AF:

0.136

Gnomad4 NFE

AF:

0.189

Gnomad4 OTH

AF:

0.172

Alfa

AF:

0.167

Hom.:

399

Bravo

AF:

0.153

TwinsUK

AF:

0.182

AC:

675

ALSPAC

AF:

0.190

AC:

732

ExAC

AF:

0.137

AC:

2558

Asia WGS

AF:

0.122

AC:

427

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.099

.;T;.;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.54

T;T;T;T

MetaRNN

Benign

0.0013

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.99

PROVEAN

Uncertain

-3.5

.;D;.;.

REVEL

Benign

0.081

Sift

Uncertain

0.017

.;D;.;.

Sift4G

Benign

0.27

.;T;T;.

Polyphen

0.0010

.;B;.;.

Vest4

0.075

MutPred

0.16

Loss of disorder (P = 0.0793);Loss of disorder (P = 0.0793);Loss of disorder (P = 0.0793);.;

ClinPred

0.035

GERP RS

1.1

Varity_R

0.26

gMVP

0.034

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over