rs1895172

Positions:

• chr5-129539040-G-A
• chr5-129539040-G-C

Variant summary

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

The NM_133638.6(ADAMTS19):​c.1328+10363G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,924 control chromosomes in the GnomAD database, including 6,785 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 0.26 (6785 hom., cov: 32)
• Consequence: ADAMTS19 NM_133638.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

Genes affected

ADAMTS19 (HGNC:17111): (ADAM metallopeptidase with thrombospondin type 1 motif 19) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) protein family. Members of the family 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 protein encoded by this gene has high sequence similarity to the protein encoded by ADAMTS16, another family member. [provided by RefSeq, Jul 2008]

ENSG00000251680 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS19	NM_133638.6	c.1328+10363G>A		intron_variant		ENST00000274487.9	NP_598377.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS19	ENST00000274487.9	c.1328+10363G>A		intron_variant		1	NM_133638.6	ENSP00000274487.5
ENSG00000251680	ENST00000503616.5	n.405-38453C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39332 AN: 151806 Hom.: 6768 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.259 AC: 39391 AN: 151924 Hom.: 6785 Cov.: 32 AF XY: 0.259 AC XY: 19246 AN XY: 74258

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.226

Alfa AF: 0.241 Hom.: 861

Bravo AF: 0.276

Asia WGS AF: 0.199 AC: 693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.017
DANN	Benign	0.51

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: rs1895172; hg19: chr5-128874733;