5-129664693-T-G

Position:

• chr5-129664693-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133638.6(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 NM_133638.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS19	NM_133638.6	c.2426-806T>G		intron_variant		ENST00000274487.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS19	ENST00000274487.9	c.2426-806T>G		intron_variant		1	NM_133638.6	P1
	ENST00000503616.5	n.404+70250A>C		intron_variant, non_coding_transcript_variant		3
	ENST00000653455.1	n.377-65607A>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.0687

Gnomad4 ASJ AF: 0.0605

Gnomad4 EAS AF: 0.0223

Gnomad4 SAS AF: 0.0929

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0880

Gnomad4 OTH AF: 0.0739

Alfa AF: 0.0832 Hom.: 595

Bravo AF: 0.0961

Asia WGS AF: 0.0680 AC: 234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.9
DANN	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs13436218; hg19: chr5-129000386;