5-5140734-C-A

Variant names:

• chr5-5140734-C-A
• NM_139056.4:c.143C>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.143C>A​(p.Pro48His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,417,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 7.1e-7 (0 hom.)
• Consequence: ADAMTS16 NM_139056.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117

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=0.0963828).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS16	NM_139056.4	c.143C>A	p.Pro48His	missense_variant	Exon 2 of 23	ENST00000274181.7	NP_620687.2
ADAMTS16	XM_047416874.1	c.143C>A	p.Pro48His	missense_variant	Exon 2 of 22		XP_047272830.1
ADAMTS16	XM_047416875.1	c.143C>A	p.Pro48His	missense_variant	Exon 2 of 20		XP_047272831.1
ADAMTS16	NR_136935.2	n.281C>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.143C>A	p.Pro48His	missense_variant	Exon 2 of 23	2	NM_139056.4	ENSP00000274181.7
ADAMTS16	ENST00000511368.5	c.143C>A	p.Pro48His	missense_variant	Exon 2 of 11	1		ENSP00000421631.1
ADAMTS16	ENST00000433402.2	n.143C>A		non_coding_transcript_exon_variant	Exon 2 of 20	1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1417452 Hom.: 0 Cov.: 34 AF XY: 0.00000143 AC XY: 1 AN XY: 701066

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: 0.0000124

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	0.092
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.7
DANN	Benign	0.69
DEOGEN2	Benign	0.0055	.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.35	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.096	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	.;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.020	N;N
REVEL	Benign	0.063
Sift	Benign	0.58	T;T
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.0	B;B
Vest4		0.23
MutPred		0.43		Loss of glycosylation at P48 (P = 0.0048);Loss of glycosylation at P48 (P = 0.0048);
MVP		0.50
MPC		0.33
ClinPred		0.024	T
GERP RS		1.5
Varity_R		0.048
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-5140847;