NM_139056.4:c.331G>C

Variant names:

• chr5-5146285-G-C
• rs766063759
• NM_139056.4:c.331G>C

Variant summary

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

The NM_139056.4(ADAMTS16):​c.331G>C​(p.Asp111His) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ADAMTS16 NM_139056.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.62

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]

ENSG00000250866 (HGNC:58093):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS16	NM_139056.4	c.331G>C	p.Asp111His	missense_variant	Exon 3 of 23	ENST00000274181.7	NP_620687.2
ADAMTS16	XM_047416874.1	c.331G>C	p.Asp111His	missense_variant	Exon 3 of 22		XP_047272830.1
ADAMTS16	XM_047416875.1	c.331G>C	p.Asp111His	missense_variant	Exon 3 of 20		XP_047272831.1
ADAMTS16	NR_136935.2	n.469G>C		non_coding_transcript_exon_variant	Exon 3 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS16	ENST00000274181.7	c.331G>C	p.Asp111His	missense_variant	Exon 3 of 23	2	NM_139056.4	ENSP00000274181.7
ADAMTS16	ENST00000511368.5	c.331G>C	p.Asp111His	missense_variant	Exon 3 of 11	1		ENSP00000421631.1
ADAMTS16	ENST00000433402.2	n.331G>C		non_coding_transcript_exon_variant	Exon 3 of 20	1
ENSG00000250866	ENST00000514848.1	n.221-3914C>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461882 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	.;T
Eigen	Benign	0.070
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.0063	T
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	.;L
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.17
Sift	Benign	0.037	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.054	B;D
Vest4		0.34
MutPred		0.53		Gain of MoRF binding (P = 0.0394);Gain of MoRF binding (P = 0.0394);
MVP		0.59
MPC		0.24
ClinPred		0.58	D
GERP RS		4.9
Varity_R		0.25
gMVP		0.43

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: rs766063759; hg19: chr5-5146398;