Variant 16-22075556-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001164579.2(MOSMO):c.176C>G(p.Pro59Arg) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000042 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MOSMO
NM_001164579.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.86

Variant links:

Genes affected

MOSMO (HGNC:27087): (modulator of smoothened) Predicted to be involved in negative regulation of smoothened signaling pathway; regulation of neuron differentiation; and regulation of protein stability. Predicted to be located in plasma membrane. Predicted to be active in Golgi apparatus and ciliary membrane. [provided by Alliance of Genome Resources, Apr 2022]

MOSMO links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MOSMO	NM_001164579.2 linkuse as main transcript	c.176C>G	p.Pro59Arg	missense_variant	2/3	ENST00000542527.7	NP_001158051.1
MOSMO	XM_047434583.1 linkuse as main transcript	c.150C>G	p.Ser50=	synonymous_variant	2/4		XP_047290539.1
MOSMO	XR_007064906.1 linkuse as main transcript	n.367C>G		non_coding_transcript_exon_variant	2/4
MOSMO	XR_007064907.1 linkuse as main transcript	n.367C>G		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOSMO	ENST00000542527.7 linkuse as main transcript	c.176C>G	p.Pro59Arg	missense_variant	2/3	5	NM_001164579.2	ENSP00000454926	P1	Q8NHV5-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152182

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00135

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:

0.0000346

AC:

AN:

144414

Hom.:

AF XY:

0.0000389

AC XY:

AN XY:

77128

show subpopulations

Gnomad AFR exome

AF:

0.000527

Gnomad AMR exome

AF:

0.0000407

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000419

AC:

AN:

1384954

Hom.:

Cov.:

AF XY:

0.0000424

AC XY:

AN XY:

683402

show subpopulations

Gnomad4 AFR exome

AF:

0.00165

Gnomad4 AMR exome

AF:

0.0000840

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:

0.0000518

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000368

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00135

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

Alfa

AF:

0.000337

Hom.:

ExAC

AF:

0.0000417

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

Jul 15, 2021

The c.176C>G (p.P59R) alteration is located in exon 2 (coding exon 2) of the C16orf52 gene. This alteration results from a C to G substitution at nucleotide position 176, causing the proline (P) at amino acid position 59 to be replaced by an arginine (R). 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

0.95

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

.;T;.;.

FATHMM_MKL

Uncertain

0.96

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.71

D;D;D;D

MutationTaster

Benign

1.0

D;D;D;D

PROVEAN

Pathogenic

-7.0

D;D;.;D

Sift

Uncertain

0.0020

D;D;.;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

.;D;.;.

Vest4

0.81

MVP

0.98

GERP RS

6.0

Varity_R

0.56

gMVP

0.95

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