chr5-129664693-T-G

Variant names:

• chr5-129664693-T-G
• rs13436218
• NM_133638.6:c.2426-806T>G

Variant summary

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

The ENST00000274487.9(ADAMTS19):​c.2426-806T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0974 in 152,028 control chromosomes in the GnomAD database, including 810 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 0.097 (810 hom., cov: 32)
• Consequence: ADAMTS19 ENST00000274487.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482
• Publications: 10 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000274487.9. 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.2426-806T>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.2426-806T>G		intron	N/A	ENSP00000274487.5
	ENSG00000251680	ENST00000503616.5	TSL:3	n.404+70250A>C		intron	N/A
	ENSG00000251680	ENST00000653455.2		n.433-65607A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0974 AC: 14790 AN: 151910 Hom.: 807 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0686

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.0223

Gnomad SAS AF: 0.0919

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0879

Gnomad OTH AF: 0.0742

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

GnomAD4 genome AF: 0.0974 AC: 14815 AN: 152028 Hom.: 810 Cov.: 32 AF XY: 0.0971 AC XY: 7216 AN XY: 74302

African (AFR) AF: 0.136 AC: 5631 AN: 41456

American (AMR) AF: 0.0687 AC: 1047 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0605 AC: 210 AN: 3472

East Asian (EAS) AF: 0.0223 AC: 115 AN: 5154

South Asian (SAS) AF: 0.0929 AC: 447 AN: 4814

European-Finnish (FIN) AF: 0.108 AC: 1146 AN: 10576

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0880 AC: 5981 AN: 67990

Other (OTH) AF: 0.0739 AC: 156 AN: 2112

Alfa AF: 0.0870 Hom.: 1807

Bravo AF: 0.0961

Asia WGS AF: 0.0680 AC: 234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.9
DANN	Benign	0.81
PhyloP100		-0.48
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: rs13436218; hg19: chr5-129000386;