rs13158524

Variant names:

• chr5-129552346-A-G
• rs13158524
• NM_133638.6:c.1372+439A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ADAMTS19 Gene-Disease associations (from GenCC):

• cardiac valvular dysplasia 2

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ENSG00000251680 (HGNC:58253):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133638.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS19	NM_133638.6	MANE Select	c.1372+439A>G		intron	N/A	NP_598377.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS19	ENST00000274487.9	TSL:1 MANE Select	c.1372+439A>G		intron	N/A	ENSP00000274487.5
	ENSG00000251680	ENST00000503616.5	TSL:3	n.405-51759T>C		intron	N/A

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

African (AFR) AF: 0.358 AC: 14803 AN: 41380

American (AMR) AF: 0.587 AC: 8903 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2191 AN: 3454

East Asian (EAS) AF: 0.528 AC: 2719 AN: 5146

South Asian (SAS) AF: 0.574 AC: 2765 AN: 4814

European-Finnish (FIN) AF: 0.635 AC: 6646 AN: 10468

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.656 AC: 44433 AN: 67752

Other (OTH) AF: 0.591 AC: 1242 AN: 2100

Alfa AF: 0.620 Hom.: 62208

Bravo AF: 0.546

Asia WGS AF: 0.483 AC: 1673 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.35
PhyloP100		0.88
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: rs13158524; hg19: chr5-128888039;