rs13158524

Positions:

• chr5-129552346-A-G
• chr5-129552346-A-T

Variant summary

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

The NM_133638.6(ADAMTS19):​c.1372+439A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 151,478 control chromosomes in the GnomAD database, including 24,825 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 0.56 (24825 hom., cov: 31)
• Consequence: ADAMTS19 NM_133638.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.883

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS19	NM_133638.6	c.1372+439A>G		intron_variant		ENST00000274487.9	NP_598377.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS19	ENST00000274487.9	c.1372+439A>G		intron_variant		1	NM_133638.6	ENSP00000274487	P1
	ENST00000503616.5	n.405-51759T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84320 AN: 151362 Hom.: 24834 Cov.: 31

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.557 AC: 84325 AN: 151478 Hom.: 24825 Cov.: 31 AF XY: 0.556 AC XY: 41129 AN XY: 73974

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.656

Gnomad4 OTH AF: 0.591

Alfa AF: 0.643 Hom.: 36086

Bravo AF: 0.546

Asia WGS AF: 0.483 AC: 1673 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.35

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: rs13158524; hg19: chr5-128888039;