NM_030957.4:c.*428A>T

Variant names:

• chr19-8580465-T-A
• rs116024095
• NM_030957.4:c.*428A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030957.4(ADAMTS10):​c.*428A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000237 in 168,952 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: ADAMTS10 NM_030957.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 1 publications found

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]

ADAMTS10 Gene-Disease associations (from GenCC):

• Weill-Marchesani syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Weill-Marchesani syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030957.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS10	NM_030957.4	MANE Select	c.*428A>T		3_prime_UTR	Exon 26 of 26	NP_112219.3	A0A0A0MQW6
	ADAMTS10	NM_001282352.2		c.*428A>T		3_prime_UTR	Exon 13 of 13	NP_001269281.1	Q9H324-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS10	ENST00000597188.6	TSL:5 MANE Select	c.*428A>T		3_prime_UTR	Exon 26 of 26	ENSP00000471851.1	A0A0A0MQW6
	ADAMTS10	ENST00000270328.8	TSL:5	c.*428A>T		3_prime_UTR	Exon 25 of 25	ENSP00000270328.4	A0A0A0MQW6
	ADAMTS10	ENST00000906412.1		c.*428A>T		3_prime_UTR	Exon 25 of 25	ENSP00000576471.1

Frequencies

GnomAD3 genomes AF: 0.0000199 AC: 3 AN: 150772 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000734

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000550 AC: 1 AN: 18180 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10610

African (AFR) AF: 0.00556 AC: 1 AN: 180

American (AMR) AF: 0.00 AC: 0 AN: 1540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 272

East Asian (EAS) AF: 0.00 AC: 0 AN: 640

South Asian (SAS) AF: 0.00 AC: 0 AN: 4000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 54

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 9690

Other (OTH) AF: 0.00 AC: 0 AN: 794

GnomAD4 genome AF: 0.0000199 AC: 3 AN: 150772 Hom.: 0 Cov.: 30 AF XY: 0.0000407 AC XY: 3 AN XY: 73650

African (AFR) AF: 0.0000734 AC: 3 AN: 40860

American (AMR) AF: 0.00 AC: 0 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5122

South Asian (SAS) AF: 0.00 AC: 0 AN: 4776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67652

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.76
PhyloP100		-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

Other links and lift over

dbSNP: rs116024095; hg19: chr19-8645349;