5-5147012-A-G

Variant names:

• chr5-5147012-A-G
• rs10512769
• NM_139056.4:c.501+557A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139056.4(ADAMTS16):​c.501+557A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,022 control chromosomes in the GnomAD database, including 1,852 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (1852 hom., cov: 32)
• Consequence: ADAMTS16 NM_139056.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS16	NM_139056.4	c.501+557A>G		intron_variant	Intron 3 of 22	ENST00000274181.7	NP_620687.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS16	ENST00000274181.7	c.501+557A>G		intron_variant	Intron 3 of 22	2	NM_139056.4	ENSP00000274181.7
ADAMTS16	ENST00000511368.5	c.501+557A>G		intron_variant	Intron 3 of 10	1		ENSP00000421631.1
ADAMTS16	ENST00000433402.2	n.501+557A>G		intron_variant	Intron 3 of 19	1
ENSG00000250866	ENST00000514848.1	n.221-4641T>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23038 AN: 151904 Hom.: 1848 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.137

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.152 AC: 23054 AN: 152022 Hom.: 1852 Cov.: 32 AF XY: 0.155 AC XY: 11489 AN XY: 74290

African (AFR) AF: 0.162 AC: 6736 AN: 41466

American (AMR) AF: 0.0999 AC: 1526 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0573 AC: 199 AN: 3470

East Asian (EAS) AF: 0.281 AC: 1447 AN: 5152

South Asian (SAS) AF: 0.112 AC: 537 AN: 4810

European-Finnish (FIN) AF: 0.203 AC: 2143 AN: 10548

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10039 AN: 67986

Other (OTH) AF: 0.137 AC: 289 AN: 2106

Alfa AF: 0.142 Hom.: 7314

Bravo AF: 0.143

Asia WGS AF: 0.212 AC: 736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.45
DANN	Benign	0.57
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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: rs10512769; hg19: chr5-5147125;