17-35764479-C-G

Variant names:

• chr17-35764479-C-G
• rs1555602370
• NM_145272.4:c.386C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145272.4(C17orf50):​c.386C>G​(p.Pro129Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,416,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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. P129L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: C17orf50 NM_145272.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.477
• Publications: 0 publications found

Genes affected

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

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]

ENSG00000271392 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3356862).

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.386C>G	p.Pro129Arg	missense	Exon 3 of 3	NP_660315.2	Q8WW18
	MMP28	NR_111988.2		n.2100+1718G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C17orf50	ENST00000605587.2	TSL:1 MANE Select	c.386C>G	p.Pro129Arg	missense	Exon 3 of 3	ENSP00000475146.1	Q8WW18
	C17orf50	ENST00000603305.1	TSL:3	c.408C>G	p.Ala136Ala	synonymous	Exon 3 of 3	ENSP00000474048.1	A0A075B7C2
	C17orf50	ENST00000604830.1	TSL:3	c.297C>G	p.Ala99Ala	synonymous	Exon 3 of 3	ENSP00000474618.1	A0A075B7E2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416918 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 701848

African (AFR) AF: 0.0000325 AC: 1 AN: 30808

American (AMR) AF: 0.00 AC: 0 AN: 39422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25126

East Asian (EAS) AF: 0.00 AC: 0 AN: 36492

South Asian (SAS) AF: 0.00 AC: 0 AN: 80750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4110

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092124

Other (OTH) AF: 0.00 AC: 0 AN: 58514

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T
Eigen	Benign	0.0040
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.51	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.48
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.34
MutPred		0.21		Gain of MoRF binding (P = 0.0068)
MVP		0.62
ClinPred		0.82	D
GERP RS		4.1
Varity_R		0.098
gMVP		0.017

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

Other links and lift over

dbSNP: rs1555602370; hg19: chr17-34091498;