chr15-100304360-G-A

Variant names:

• chr15-100304360-G-A
• rs12437971
• NM_139057.4:c.617-22959C>T

Variant summary

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

The NM_139057.4(ADAMTS17):​c.617-22959C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 152,078 control chromosomes in the GnomAD database, including 33,060 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 0.65 (33060 hom., cov: 32)
• Consequence: ADAMTS17 NM_139057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548
• Publications: 6 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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS17	NM_139057.4	c.617-22959C>T		intron_variant	Intron 3 of 21	ENST00000268070.9	NP_620688.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS17	ENST00000268070.9	c.617-22959C>T		intron_variant	Intron 3 of 21	1	NM_139057.4	ENSP00000268070.4
ADAMTS17	ENST00000568565.2	c.617-22959C>T		intron_variant	Intron 3 of 22	5		ENSP00000456161.2
ADAMTS17	ENST00000378898.8	n.298-22959C>T		intron_variant	Intron 2 of 14	2
ADAMTS17	ENST00000558960.1	n.*39-22959C>T		intron_variant	Intron 2 of 3	2		ENSP00000453604.1

Frequencies

GnomAD3 genomes AF: 0.645 AC: 98066 AN: 151960 Hom.: 33004 Cov.: 32

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.646 AC: 98186 AN: 152078 Hom.: 33060 Cov.: 32 AF XY: 0.649 AC XY: 48256 AN XY: 74352

African (AFR) AF: 0.838 AC: 34772 AN: 41488

American (AMR) AF: 0.664 AC: 10157 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1727 AN: 3468

East Asian (EAS) AF: 0.564 AC: 2912 AN: 5164

South Asian (SAS) AF: 0.743 AC: 3579 AN: 4818

European-Finnish (FIN) AF: 0.557 AC: 5896 AN: 10580

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.545 AC: 37056 AN: 67950

Other (OTH) AF: 0.625 AC: 1322 AN: 2114

Alfa AF: 0.573 Hom.: 34841

Bravo AF: 0.657

Asia WGS AF: 0.696 AC: 2420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.16
DANN	Benign	0.68
PhyloP100		-0.55
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: rs12437971; hg19: chr15-100844565;