15-100044613-A-G

Variant names:

• chr15-100044613-A-G
• rs4965273
• NM_139057.4:c.2591+4244T>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.2591+4244T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,982 control chromosomes in the GnomAD database, including 10,665 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 0.35 (10665 hom., cov: 32)
• Consequence: ADAMTS17 NM_139057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.541 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS17	NM_139057.4	MANE Select	c.2591+4244T>C		intron	N/A	NP_620688.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS17	ENST00000268070.9	TSL:1 MANE Select	c.2591+4244T>C		intron	N/A	ENSP00000268070.4
	ADAMTS17	ENST00000961098.1		c.2741+4244T>C		intron	N/A	ENSP00000631157.1
	ADAMTS17	ENST00000568565.2	TSL:5	c.2672+4244T>C		intron	N/A	ENSP00000456161.2

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52546 AN: 151864 Hom.: 10643 Cov.: 32

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.346 AC: 52618 AN: 151982 Hom.: 10665 Cov.: 32 AF XY: 0.348 AC XY: 25850 AN XY: 74296

African (AFR) AF: 0.547 AC: 22640 AN: 41414

American (AMR) AF: 0.414 AC: 6315 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 893 AN: 3470

East Asian (EAS) AF: 0.491 AC: 2530 AN: 5154

South Asian (SAS) AF: 0.268 AC: 1293 AN: 4826

European-Finnish (FIN) AF: 0.238 AC: 2516 AN: 10576

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15482 AN: 67966

Other (OTH) AF: 0.342 AC: 724 AN: 2114

Alfa AF: 0.284 Hom.: 994

Bravo AF: 0.373

Asia WGS AF: 0.438 AC: 1523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.9
DANN	Benign	0.72
PhyloP100		-0.18
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: rs4965273; hg19: chr15-100584818;