Genetic Variant C17orf50:p.Pro119Leu (chr17-35764449-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145272.4(C17orf50):c.356C>T(p.Pro119Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000483 in 1,553,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

C17orf50
NM_145272.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.502

Variant links:

Genes affected

C17orf50 (HGNC:29581): (chromosome 17 open reading frame 50)

C17orf50 links:

MMP28 (HGNC:14366): (matrix metallopeptidase 28) Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix for both normal physiological processes, such as embryonic development, reproduction and tissue remodeling, and disease processes, such as asthma and metastasis. This gene encodes a secreted enzyme that degrades casein. Its expression pattern suggests that it plays a role in tissue homeostasis and in wound repair. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2014]

MMP28 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=0.012937754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C17orf50	NM_145272.4 link	c.356C>T	p.Pro119Leu	missense_variant	Exon 3 of 3	ENST00000605587.2	NP_660315.2	Q8WW18
MMP28	XM_011525231.2 link	c.1168+3303G>A		intron_variant	Intron 7 of 7		XP_011523533.1
MMP28	XM_017025064.2 link	c.*27+3303G>A		intron_variant	Intron 7 of 7		XP_016880553.1
MMP28	NR_111988.2 link	n.2100+1748G>A		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C17orf50	ENST00000605587.2 link	c.356C>T	p.Pro119Leu	missense_variant	Exon 3 of 3	1	NM_145272.4	ENSP00000475146.1		Q8WW18

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000701

AC:

AN:

156976

Hom.:

AF XY:

0.0000809

AC XY:

AN XY:

86548

show subpopulations

Gnomad AFR exome

AF:

0.000489

Gnomad AMR exome

AF:

0.000156

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000934

Gnomad SAS exome

AF:

0.0000437

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000157

Gnomad OTH exome

AF:

0.000238

GnomAD4 exome

AF:

0.0000235

AC:

AN:

1401488

Hom.:

Cov.:

AF XY:

0.0000245

AC XY:

AN XY:

693062

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.000108

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000113

Gnomad4 SAS exome

AF:

0.0000378

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000518

GnomAD4 genome

AF:

0.000276

AC:

AN:

152088

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.000917

Gnomad4 AMR

AF:

0.000262

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:

0.0000283

Hom.:

Bravo

AF:

0.000276

ExAC

AF:

0.0000782

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 05, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.356C>T (p.P119L) alteration is located in exon 3 (coding exon 3) of the C17orf50 gene. This alteration results from a C to T substitution at nucleotide position 356, causing the proline (P) at amino acid position 119 to be replaced by a leucine (L). 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

0.11

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.58

CADD

Benign

4.0

DANN

Benign

0.90

DEOGEN2

Benign

0.044

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.45

M_CAP

Benign

0.029

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

Sift4G

Benign

1.0

Polyphen

0.010

Vest4

0.11

MVP

0.040

ClinPred

0.0092

GERP RS

-2.7

Varity_R

0.047

gMVP

0.014

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