NM_133638.6:c.3313-13866G>T

Variant names:

• chr5-129721066-G-T
• rs246246
• NM_133638.6:c.3313-13866G>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.3313-13866G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.943 in 152,300 control chromosomes in the GnomAD database, including 67,797 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 0.94 (67797 hom., cov: 32)
• Consequence: ADAMTS19 NM_133638.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363
• Publications: 5 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS19	NM_133638.6	c.3313-13866G>T		intron_variant	Intron 21 of 22	ENST00000274487.9	NP_598377.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS19	ENST00000274487.9	c.3313-13866G>T		intron_variant	Intron 21 of 22	1	NM_133638.6	ENSP00000274487.5
ENSG00000251680	ENST00000503616.5	n.404+13877C>A		intron_variant	Intron 4 of 4	3
ADAMTS19	ENST00000509467.1	n.610-13866G>T		intron_variant	Intron 4 of 4	3
ENSG00000251680	ENST00000653455.2	n.432+13877C>A		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.943 AC: 143474 AN: 152182 Hom.: 67742 Cov.: 32

Gnomad AFR AF: 0.986

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.951

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.910

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.920

Gnomad OTH AF: 0.954

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

GnomAD4 genome AF: 0.943 AC: 143588 AN: 152300 Hom.: 67797 Cov.: 32 AF XY: 0.941 AC XY: 70083 AN XY: 74470

African (AFR) AF: 0.987 AC: 41030 AN: 41590

American (AMR) AF: 0.951 AC: 14543 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 3329 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5182 AN: 5188

South Asian (SAS) AF: 0.910 AC: 4386 AN: 4820

European-Finnish (FIN) AF: 0.887 AC: 9402 AN: 10600

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.920 AC: 62568 AN: 68018

Other (OTH) AF: 0.955 AC: 2018 AN: 2114

Alfa AF: 0.924 Hom.: 33175

Bravo AF: 0.951

Asia WGS AF: 0.952 AC: 3312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.40
DANN	Benign	0.34
PhyloP100		-0.36
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: rs246246; hg19: chr5-129056759;