chr5-5140746-C-A

Variant names:

• chr5-5140746-C-A
• rs1018938800
• NM_139056.4:c.155C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139056.4(ADAMTS16):​c.155C>A​(p.Pro52Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADAMTS16 NM_139056.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185

Genes affected

ADAMTS16 (HGNC:17108): (ADAM metallopeptidase with thrombospondin type 1 motif 16) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. ADAMTS family members share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature protein, which may inhibit chondrosarcoma cell proliferation and migration. This gene may regulate blood pressure. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.086856455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS16	NM_139056.4	c.155C>A	p.Pro52Gln	missense_variant	Exon 2 of 23	ENST00000274181.7	NP_620687.2
ADAMTS16	XM_047416874.1	c.155C>A	p.Pro52Gln	missense_variant	Exon 2 of 22		XP_047272830.1
ADAMTS16	XM_047416875.1	c.155C>A	p.Pro52Gln	missense_variant	Exon 2 of 20		XP_047272831.1
ADAMTS16	NR_136935.2	n.293C>A		non_coding_transcript_exon_variant	Exon 2 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS16	ENST00000274181.7	c.155C>A	p.Pro52Gln	missense_variant	Exon 2 of 23	2	NM_139056.4	ENSP00000274181.7
ADAMTS16	ENST00000511368.5	c.155C>A	p.Pro52Gln	missense_variant	Exon 2 of 11	1		ENSP00000421631.1
ADAMTS16	ENST00000433402.2	n.155C>A		non_coding_transcript_exon_variant	Exon 2 of 20	1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000586 AC: 1 AN: 170700 Hom.: 0 AF XY: 0.0000108 AC XY: 1 AN XY: 92766

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000740

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1414020 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 699040

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Benign	0.80
DEOGEN2	Benign	0.017	.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.087	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	.;L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.30	N;N
REVEL	Benign	0.050
Sift	Benign	0.69	T;T
Sift4G	Benign	0.096	T;T
Polyphen		0.31	B;B
Vest4		0.31
MutPred		0.33		Loss of glycosylation at P52 (P = 0.0544);Loss of glycosylation at P52 (P = 0.0544);
MVP		0.50
MPC		0.18
ClinPred		0.069	T
GERP RS		-1.5
Varity_R		0.051
gMVP		0.30

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

Other links and lift over

dbSNP: rs1018938800; hg19: chr5-5140859;