Variant chr16-85708063-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000284245.9(C16orf74):c.176G>C(p.Trp59Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,553,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

C16orf74
ENST00000284245.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.43

Variant links:

Genes affected

C16orf74 (HGNC:23362): (chromosome 16 open reading frame 74)

C16orf74 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38861346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
C16orf74	NM_206967.3 linkuse as main transcript	c.176G>C	p.Trp59Ser	missense_variant	4/4	ENST00000284245.9	NP_996850.1
C16orf74	NR_161452.1 linkuse as main transcript	n.407G>C		non_coding_transcript_exon_variant	5/5
C16orf74	NR_161453.1 linkuse as main transcript	n.221G>C		non_coding_transcript_exon_variant	3/3
C16orf74	NR_161454.1 linkuse as main transcript	n.343G>C		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C16orf74	ENST00000284245.9 linkuse as main transcript	c.176G>C	p.Trp59Ser	missense_variant	4/4	1	NM_206967.3	ENSP00000284245	P1	Q96GX8-1
	ENST00000655120.1 linkuse as main transcript	n.348-1476C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000634

AC:

AN:

157782

Hom.:

AF XY:

0.00

AC XY:

AN XY:

83562

show subpopulations

Gnomad AFR exome

AF:

0.000120

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000500

AC:

AN:

1400968

Hom.:

Cov.:

AF XY:

0.00000723

AC XY:

AN XY:

691148

show subpopulations

Gnomad4 AFR exome

AF:

0.000221

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000216

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.000252

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000190

AC:

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

Nov 05, 2021

The c.176G>C (p.W59S) alteration is located in exon 4 (coding exon 3) of the C16orf74 gene. This alteration results from a G to C substitution at nucleotide position 176, causing the tryptophan (W) at amino acid position 59 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

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.16

.;.;T;.;.

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.52

T;.;T;T;T

M_CAP

Benign

0.063

MetaRNN

Benign

0.39

T;T;T;T;T

MetaSVM

Benign

-0.79

MutationTaster

Benign

1.0

PROVEAN

Pathogenic

-9.6

.;.;D;.;.

REVEL

Benign

0.26

Sift

Uncertain

0.010

.;.;D;.;.

Sift4G

Benign

0.073

T;D;T;D;D

Polyphen

0.90

.;.;P;.;.

Vest4

0.57

MVP

0.55

MPC

0.010

ClinPred

0.94

GERP RS

4.6

Varity_R

0.66

gMVP

0.022

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