NM_139057.4:c.1075+8070T>C

Variant names:

• chr15-100246066-A-G
• rs4533267
• NM_139057.4:c.1075+8070T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139057.4(ADAMTS17):​c.1075+8070T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 151,994 control chromosomes in the GnomAD database, including 32,441 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 0.64 (32441 hom., cov: 32)
• Consequence: ADAMTS17 NM_139057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255
• Publications: 38 publications found

Genes affected

ADAMTS17 (HGNC:17109): (ADAM metallopeptidase with thrombospondin type 1 motif 17) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. ADAMTS family members 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 encoded preproprotein is proteolytically processed to generate the mature protein, which may promote breast cancer cell growth and survival. Mutations in this gene are associated with a Weill-Marchesani-like syndrome, which is characterized by lenticular myopia, ectopia lentis, glaucoma, spherophakia, and short stature. [provided by RefSeq, May 2016]

ADAMTS17 Gene-Disease associations (from GenCC):

• Weill-Marchesani 4 syndrome, recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P, Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139057.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS17	NM_139057.4	MANE Select	c.1075+8070T>C		intron	N/A	NP_620688.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS17	ENST00000268070.9	TSL:1 MANE Select	c.1075+8070T>C		intron	N/A	ENSP00000268070.4
	ADAMTS17	ENST00000568565.2	TSL:5	c.1075+8070T>C		intron	N/A	ENSP00000456161.2
	ADAMTS17	ENST00000378898.8	TSL:2	n.756+8070T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97271 AN: 151876 Hom.: 32439 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.637

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

GnomAD4 genome AF: 0.640 AC: 97314 AN: 151994 Hom.: 32441 Cov.: 32 AF XY: 0.645 AC XY: 47940 AN XY: 74286

African (AFR) AF: 0.441 AC: 18271 AN: 41434

American (AMR) AF: 0.666 AC: 10173 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2146 AN: 3468

East Asian (EAS) AF: 0.798 AC: 4125 AN: 5166

South Asian (SAS) AF: 0.778 AC: 3725 AN: 4790

European-Finnish (FIN) AF: 0.754 AC: 7974 AN: 10570

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48705 AN: 67968

Other (OTH) AF: 0.639 AC: 1347 AN: 2108

Alfa AF: 0.690 Hom.: 171524

Bravo AF: 0.621

Asia WGS AF: 0.741 AC: 2580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.31
PhyloP100		-0.26
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: rs4533267; hg19: chr15-100786271;