5-129605207-T-C

Variant names:

• chr5-129605207-T-C
• rs1972624
• NM_133638.6:c.1478+8543T>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.1478+8543T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,976 control chromosomes in the GnomAD database, including 27,218 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 0.58 (27218 hom., cov: 32)
• Consequence: ADAMTS19 NM_133638.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.729
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS19	NM_133638.6	c.1478+8543T>C		intron_variant	Intron 8 of 22	ENST00000274487.9	NP_598377.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS19	ENST00000274487.9	c.1478+8543T>C		intron_variant	Intron 8 of 22	1	NM_133638.6	ENSP00000274487.5
ENSG00000251680	ENST00000503616.5	n.405-104620A>G		intron_variant	Intron 4 of 4	3
ENSG00000251680	ENST00000653455.2	n.433-6121A>G		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88478 AN: 151858 Hom.: 27227 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.582 AC: 88495 AN: 151976 Hom.: 27218 Cov.: 32 AF XY: 0.583 AC XY: 43323 AN XY: 74296

African (AFR) AF: 0.369 AC: 15306 AN: 41448

American (AMR) AF: 0.606 AC: 9238 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2238 AN: 3468

East Asian (EAS) AF: 0.601 AC: 3100 AN: 5156

South Asian (SAS) AF: 0.623 AC: 3002 AN: 4818

European-Finnish (FIN) AF: 0.666 AC: 7053 AN: 10588

Middle Eastern (MID) AF: 0.562 AC: 164 AN: 292

European-Non Finnish (NFE) AF: 0.686 AC: 46610 AN: 67944

Other (OTH) AF: 0.608 AC: 1282 AN: 2108

Alfa AF: 0.551 Hom.: 3029

Bravo AF: 0.569

Asia WGS AF: 0.550 AC: 1914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.15
DANN	Benign	0.41
PhyloP100		-0.73
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: rs1972624; hg19: chr5-128940900;