rs2964433

Positions:

• chr5-5237484-G-A
• chr5-5237484-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139056.4(ADAMTS16):​c.2154+385G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,116 control chromosomes in the GnomAD database, including 1,211 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 0.12 (1211 hom., cov: 32)
• Consequence: ADAMTS16 NM_139056.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.953

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]

ADAMTS16 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS16	NM_139056.4	c.2154+385G>A		intron_variant		ENST00000274181.7	NP_620687.2
ADAMTS16	XM_047416874.1	c.2154+385G>A		intron_variant			XP_047272830.1
ADAMTS16	XM_047416875.1	c.2154+385G>A		intron_variant			XP_047272831.1
ADAMTS16	NR_136935.2	n.2162-1667G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS16	ENST00000274181.7	c.2154+385G>A		intron_variant		2	NM_139056.4	ENSP00000274181.7
ADAMTS16	ENST00000433402.2	n.2154+385G>A		intron_variant		1
ADAMTS16	ENST00000513709.1	n.151-1667G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18407 AN: 151998 Hom.: 1210 Cov.: 32

Gnomad AFR AF: 0.0756

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0918

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0926

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.121 AC: 18418 AN: 152116 Hom.: 1211 Cov.: 32 AF XY: 0.122 AC XY: 9058 AN XY: 74366

Gnomad4 AFR AF: 0.0755

Gnomad4 AMR AF: 0.0919

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.0929

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.121

Alfa AF: 0.130 Hom.: 213

Bravo AF: 0.112

Asia WGS AF: 0.148 AC: 512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.65
DANN	Benign	0.68

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: rs2964433; hg19: chr5-5237597;