Variant 19-50658065-G-C 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_001195076.2(C19orf81):c.338G>C(p.Arg113Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,536,016 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00093 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

C19orf81
NM_001195076.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.500

Variant links:

Genes affected

C19orf81 (HGNC:40041): (chromosome 19 open reading frame 81)

C19orf81 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=0.008629888).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C19orf81	NM_001195076.2 linkuse as main transcript	c.338G>C	p.Arg113Pro	missense_variant	4/5	ENST00000425202.6	NP_001182005.1
C19orf81	XM_047438759.1 linkuse as main transcript	c.320G>C	p.Arg107Pro	missense_variant	4/5		XP_047294715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C19orf81	ENST00000425202.6 linkuse as main transcript	c.338G>C	p.Arg113Pro	missense_variant	4/5	5	NM_001195076.2	ENSP00000417035	P1
C19orf81	ENST00000458538.1 linkuse as main transcript	c.260G>C	p.Arg87Pro	missense_variant	4/5	3		ENSP00000391035

Frequencies

GnomAD3 genomes

AF:

0.000933

AC:

142

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00302

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000216

AC:

AN:

134328

Hom.:

AF XY:

0.000109

AC XY:

AN XY:

73156

show subpopulations

Gnomad AFR exome

AF:

0.00280

Gnomad AMR exome

AF:

0.000409

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:

0.00

Gnomad OTH exome

AF:

0.000243

GnomAD4 exome

AF:

0.0000860

AC:

119

AN:

1383692

Hom.:

Cov.:

AF XY:

0.0000600

AC XY:

AN XY:

682790

show subpopulations

Gnomad4 AFR exome

AF:

0.00279

Gnomad4 AMR exome

AF:

0.000448

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:

0.00000185

Gnomad4 OTH exome

AF:

0.000225

GnomAD4 genome

AF:

0.000932

AC:

142

AN:

152324

Hom.:

Cov.:

AF XY:

0.000765

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00301

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.00111

ExAC

AF:

0.000145

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Sep 17, 2021

The c.338G>C (p.R113P) alteration is located in exon 4 (coding exon 4) of the C19orf81 gene. This alteration results from a G to C substitution at nucleotide position 338, causing the arginine (R) at amino acid position 113 to be replaced by a proline (P). 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

Pathogenic

0.72

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.0086

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

0.97

N;D

PROVEAN

Uncertain

-4.3

D;.

REVEL

Benign

0.26

Sift

Uncertain

0.022

D;.

Sift4G

Benign

0.072

T;T

Vest4

0.63

MutPred

0.32

Loss of sheet (P = 0.0357);.;

MVP

0.15

ClinPred

0.078

GERP RS

2.7

Varity_R

0.60

gMVP

0.39

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