Genetic Variant NM_145272.4:c.511G>T (chr17-35764604-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_145272.4(C17orf50):c.511G>T(p.Ala171Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,584,388 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A171P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

C17orf50
NM_145272.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.550

Publications

2 publications found

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:

ENSG00000271392 (HGNC:):

ENSG00000271392 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003054738).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145272.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C17orf50	NM_145272.4	MANE Select	c.511G>T	p.Ala171Ser	missense	Exon 3 of 3	NP_660315.2	Q8WW18
	MMP28	NR_111988.2		n.2100+1593C>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C17orf50	ENST00000605587.2	TSL:1 MANE Select	c.511G>T	p.Ala171Ser	missense	Exon 3 of 3	ENSP00000475146.1	Q8WW18
C17orf50	ENST00000604830.1	TSL:3	c.*11G>T		3_prime_UTR	Exon 3 of 3	ENSP00000474618.1	A0A075B7E2
MMP28	ENST00000615317.4	TSL:2	c.265+3148C>A		intron	N/A	ENSP00000482385.1	A0A087WZ56

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000237

AC:

AN:

211256

AF XY:

0.000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000138

Gnomad ASJ exome

AF:

0.00397

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000103

Gnomad OTH exome

AF:

0.000204

GnomAD4 exome

AF:

0.000145

AC:

207

AN:

1432204

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

105

AN XY:

712498

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30170

American (AMR)

AF:

0.0000736

AC:

AN:

40780

Ashkenazi Jewish (ASJ)

AF:

0.00328

AC:

AN:

25278

East Asian (EAS)

AF:

0.00

AC:

AN:

36460

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82870

European-Finnish (FIN)

AF:

0.0000385

AC:

AN:

51892

Middle Eastern (MID)

AF:

0.000733

AC:

AN:

4090

European-Non Finnish (NFE)

AF:

0.0000817

AC:

AN:

1101614

Other (OTH)

AF:

0.000423

AC:

AN:

59050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000177

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68030

Other (OTH)

AF:

0.000955

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000575

Hom.:

Bravo

AF:

0.000189

ExAC

AF:

0.000183

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.1

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.00047

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.33

M_CAP

Benign

0.017

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

-0.55

PrimateAI

Benign

0.32

Sift4G

Benign

0.72

Polyphen

0.041

Vest4

0.031

MutPred

0.14

Gain of glycosylation at A171 (P = 0.0069)

MVP

0.040

ClinPred

0.043

GERP RS

-7.6

Varity_R

0.13

gMVP

0.011

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over