rs34057037

Variant names:

• chr19-8580436-ACC-A
• rs34057037
• NM_030957.4:c.*455_*456delGG

Your query was ambiguous. Multiple possible variants found:

• chr19-8580436-ACC-A
• chr19-8580436-ACC-AC
• chr19-8580436-ACC-ACCC
• chr19-8580436-ACC-ACCCC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_030957.4(ADAMTS10):​c.*455_*456delGG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 151,708 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00066 (0 hom., cov: 0)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: ADAMTS10 NM_030957.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262

Genes affected

ADAMTS10 (HGNC:13201): (ADAM metallopeptidase with thrombospondin type 1 motif 10) This gene belongs to the ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin type-1 motifs) family of zinc-dependent proteases. ADAMTS proteases are complex secreted enzymes containing a prometalloprotease domain of the reprolysin type attached to an ancillary domain with a highly conserved structure that includes at least one thrombospondin type 1 repeat. They have been demonstrated to have important roles in connective tissue organization, coagulation, inflammation, arthritis, angiogenesis and cell migration. The product of this gene plays a major role in growth and in skin, lens, and heart development. It is also a candidate gene for autosomal recessive Weill-Marchesani syndrome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00066 (93/140828) while in subpopulation AFR AF= 0.000904 (34/37610). AF 95% confidence interval is 0.000665. There are 0 homozygotes in gnomad4. There are 49 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS10	NM_030957.4	c.*455_*456delGG		3_prime_UTR_variant	Exon 26 of 26	ENST00000597188.6	NP_112219.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS10	ENST00000597188	c.*455_*456delGG		3_prime_UTR_variant	Exon 26 of 26	5	NM_030957.4	ENSP00000471851.1
ADAMTS10	ENST00000270328	c.*455_*456delGG		3_prime_UTR_variant	Exon 25 of 25	5		ENSP00000270328.4
ADAMTS10	ENST00000595838	c.*455_*456delGG		3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000470501.1

Frequencies

GnomAD3 genomes AF: 0.000661 AC: 93 AN: 140752 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000907

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000210

Gnomad ASJ AF: 0.0105

Gnomad EAS AF: 0.000408

Gnomad SAS AF: 0.000226

Gnomad FIN AF: 0.000208

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000252

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0109 AC: 119 AN: 10880 Hom.: 0 AF XY: 0.0116 AC XY: 72 AN XY: 6228

Gnomad4 AFR exome AF: 0.0250

Gnomad4 AMR exome AF: 0.0129

Gnomad4 ASJ exome AF: 0.0410

Gnomad4 EAS exome AF: 0.0271

Gnomad4 SAS exome AF: 0.00995

Gnomad4 FIN exome AF: 0.00467

Gnomad4 NFE exome AF: 0.00879

Gnomad4 OTH exome AF: 0.0222

GnomAD4 genome AF: 0.000660 AC: 93 AN: 140828 Hom.: 0 Cov.: 0 AF XY: 0.000714 AC XY: 49 AN XY: 68650

Gnomad4 AFR AF: 0.000904

Gnomad4 AMR AF: 0.000210

Gnomad4 ASJ AF: 0.0105

Gnomad4 EAS AF: 0.000409

Gnomad4 SAS AF: 0.000227

Gnomad4 FIN AF: 0.000208

Gnomad4 NFE AF: 0.000252

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs34057037; hg19: chr19-8645320;