NM_145272.4:c.314T>C

Variant names:

• chr17-35764307-T-C
• rs782385657
• NM_145272.4:c.314T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_145272.4(C17orf50):​c.314T>C​(p.Leu105Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,494,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: C17orf50 NM_145272.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09594777).

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.314T>C	p.Leu105Pro	missense	Exon 2 of 3	NP_660315.2	Q8WW18
	MMP28	NR_111988.2		n.2100+1890A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C17orf50	ENST00000605587.2	TSL:1 MANE Select	c.314T>C	p.Leu105Pro	missense	Exon 2 of 3	ENSP00000475146.1	Q8WW18
	C17orf50	ENST00000603305.1	TSL:3	c.336T>C	p.Pro112Pro	synonymous	Exon 2 of 3	ENSP00000474048.1	A0A075B7C2
	C17orf50	ENST00000604830.1	TSL:3	c.243+71T>C		intron	N/A	ENSP00000474618.1	A0A075B7E2

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 151862 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000202 AC: 19 AN: 94264 AF XY: 0.000232

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000114

Gnomad ASJ exome AF: 0.000205

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000518

Gnomad NFE exome AF: 0.000306

Gnomad OTH exome AF: 0.000345

GnomAD4 exome AF: 0.000215 AC: 289 AN: 1342916 Hom.: 0 Cov.: 31 AF XY: 0.000209 AC XY: 138 AN XY: 658930

African (AFR) AF: 0.0000711 AC: 2 AN: 28126

American (AMR) AF: 0.000104 AC: 3 AN: 28962

Ashkenazi Jewish (ASJ) AF: 0.000358 AC: 8 AN: 22372

East Asian (EAS) AF: 0.0000297 AC: 1 AN: 33624

South Asian (SAS) AF: 0.00 AC: 0 AN: 71998

European-Finnish (FIN) AF: 0.000433 AC: 17 AN: 39228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3972

European-Non Finnish (NFE) AF: 0.000231 AC: 245 AN: 1058972

Other (OTH) AF: 0.000234 AC: 13 AN: 55662

GnomAD4 genome AF: 0.000145 AC: 22 AN: 151862 Hom.: 0 Cov.: 32 AF XY: 0.000162 AC XY: 12 AN XY: 74182

African (AFR) AF: 0.0000242 AC: 1 AN: 41340

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67920

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.000262 Hom.: 0

Bravo AF: 0.000113

ExAC AF: 0.0000292 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Benign	0.82
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.40	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.0
Sift4G	Pathogenic	0.0	D
Polyphen		0.56	P
Vest4		0.32
MutPred		0.32		Gain of relative solvent accessibility (P = 0.0104)
MVP		0.27
ClinPred		0.057	T
GERP RS		4.4
Varity_R		0.22
gMVP		0.064
Mutation Taster		=100/0	polymorphism

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: rs782385657; hg19: chr17-34091326;