rs199950029

Variant names:

• chr17-35764604-G-A
• rs199950029
• NM_145272.4:c.511G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-35764604-G-A
• chr17-35764604-G-C
• chr17-35764604-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145272.4(C17orf50):​c.511G>A​(p.Ala171Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000419 in 1,432,204 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. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: C17orf50 NM_145272.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550
• Publications: 2 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028582156).

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>A	p.Ala171Thr	missense	Exon 3 of 3	NP_660315.2	Q8WW18
	MMP28	NR_111988.2		n.2100+1593C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C17orf50	ENST00000605587.2	TSL:1 MANE Select	c.511G>A	p.Ala171Thr	missense	Exon 3 of 3	ENSP00000475146.1	Q8WW18
	C17orf50	ENST00000604830.1	TSL:3	c.*11G>A		3_prime_UTR	Exon 3 of 3	ENSP00000474618.1	A0A075B7E2
	MMP28	ENST00000615317.4	TSL:2	c.265+3148C>T		intron	N/A	ENSP00000482385.1	A0A087WZ56

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 211256 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000419 AC: 6 AN: 1432204 Hom.: 0 Cov.: 31 AF XY: 0.00000281 AC XY: 2 AN XY: 712498

African (AFR) AF: 0.0000331 AC: 1 AN: 30170

American (AMR) AF: 0.00 AC: 0 AN: 40780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25280

East Asian (EAS) AF: 0.00 AC: 0 AN: 36460

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82870

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51892

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4090

European-Non Finnish (NFE) AF: 0.00000272 AC: 3 AN: 1101612

Other (OTH) AF: 0.0000169 AC: 1 AN: 59050

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000832 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.0
DANN	Benign	0.95
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.55
Sift4G	Benign	0.76	T
Polyphen		0.086	B
Vest4		0.029
MutPred		0.13		Gain of glycosylation at A171 (P = 0.0092)
MVP		0.040
ClinPred		0.76	D
GERP RS		-7.6
Varity_R		0.079
gMVP		0.013
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs199950029; hg19: chr17-34091623;