rs246246

chr5-129721066-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.99).
• 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/exons	MANE	UniProt
ADAMTS19	NM_133638.6	c.3313-13866G>T		intron_variant		ENST00000274487.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS19	ENST00000274487.9	c.3313-13866G>T		intron_variant		1	NM_133638.6	P1
	ENST00000503616.5	n.404+13877C>A		intron_variant, non_coding_transcript_variant		3
ADAMTS19	ENST00000509467.1	n.610-13866G>T		intron_variant, non_coding_transcript_variant		3
	ENST00000653455.1	n.376+13877C>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.987

Gnomad4 AMR AF: 0.951

Gnomad4 ASJ AF: 0.959

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.910

Gnomad4 FIN AF: 0.887

Gnomad4 NFE AF: 0.920

Gnomad4 OTH AF: 0.955

Alfa AF: 0.923 Hom.: 29475

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

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: rs246246; hg19: chr5-129056759;