rs1895172

Variant names:

• chr5-129539040-G-A
• rs1895172
• NM_133638.6:c.1328+10363G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 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.1328+10363G>A		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.1328+10363G>A		intron	N/A	ENSP00000274487.5
	ENSG00000251680	ENST00000503616.5	TSL:3	n.405-38453C>T		intron	N/A

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

African (AFR) AF: 0.489 AC: 20235 AN: 41416

American (AMR) AF: 0.230 AC: 3499 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 912 AN: 3468

East Asian (EAS) AF: 0.113 AC: 585 AN: 5172

South Asian (SAS) AF: 0.192 AC: 922 AN: 4814

European-Finnish (FIN) AF: 0.196 AC: 2067 AN: 10572

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10388 AN: 67928

Other (OTH) AF: 0.226 AC: 475 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.017
DANN	Benign	0.51
PhyloP100		-1.3
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: rs1895172; hg19: chr5-128874733; COSMIC: COSV107281405;