Genetic Variant C20orf96:p.Leu142Val (chr20-279213-G-C) – 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_153269.3(C20orf96):c.424C>G(p.Leu142Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,609,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

C20orf96
NM_153269.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.981

Variant links:

Genes affected

C20orf96 (HGNC:16227): (chromosome 20 open reading frame 96)

C20orf96 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=0.095124245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C20orf96	NM_153269.3 link	c.424C>G	p.Leu142Val	missense_variant	Exon 5 of 11	ENST00000360321.7	NP_695001.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
C20orf96	ENST00000360321.7 link	c.424C>G	p.Leu142Val	missense_variant	Exon 5 of 11	1	NM_153269.3	ENSP00000353470.2	Q9NUD7
C20orf96	ENST00000400269.4 link	c.421C>G	p.Leu141Val	missense_variant	Exon 5 of 11	1		ENSP00000383128.4	F5GZA9
C20orf96	ENST00000382369.9 link	c.319C>G	p.Leu107Val	missense_variant	Exon 3 of 9	5		ENSP00000371806.5	Q5JYC3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151836

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000163

AC:

AN:

244700

Hom.:

AF XY:

0.0000226

AC XY:

AN XY:

132982

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

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:

0.0000272

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000240

AC:

AN:

1457250

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

725258

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

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:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151836

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74156

show subpopulations

Gnomad4 AFR

AF:

0.0000726

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000456

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.424C>G (p.L142V) alteration is located in exon 5 (coding exon 5) of the C20orf96 gene. This alteration results from a C to G substitution at nucleotide position 424, causing the leucine (L) at amino acid position 142 to be replaced by a valine (V). 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

0.076

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.64

CADD

Benign

4.8

DANN

Benign

0.97

DEOGEN2

Benign

0.028

.;T;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.60

T;T;T

M_CAP

Benign

0.0095

MetaRNN

Benign

0.095

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.1

.;M;.

PROVEAN

Benign

-0.94

N;N;.

REVEL

Benign

0.033

Sift

Benign

0.23

T;T;.

Sift4G

Benign

0.28

T;T;T

Polyphen

0.95

P;P;.

Vest4

0.23

MutPred

0.24

.;Gain of glycosylation at T141 (P = 0.0745);.;

MVP

0.20

MPC

0.21

ClinPred

0.14

GERP RS

-1.1

Varity_R

0.050

gMVP

0.059

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