11-130405451-G-C

Variant names:

• chr11-130405451-G-C
• rs2242312
• NM_007037.6:c.*107C>G

Variant summary

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

The NM_007037.6(ADAMTS8):​c.*107C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000028 in 1,498,342 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: 32)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: ADAMTS8 NM_007037.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129
• Publications: 9 publications found

Genes affected

ADAMTS8 (HGNC:224): (ADAM metallopeptidase with thrombospondin type 1 motif 8) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family 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 enzyme. This enzyme contains two C-terminal TS motifs, and disrupts angiogenesis in vivo. A number of disorders have been mapped in the vicinity of this gene, most notably lung neoplasms. Reduced expression of this gene has been observed in multiple human cancers and this gene has been proposed as a potential tumor suppressor. [provided by RefSeq, Feb 2016]

ZBTB44-DT (HGNC:54265): (ZBTB44 divergent transcript)

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=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007037.6. 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
	ADAMTS8	NM_007037.6	MANE Select	c.*107C>G		3_prime_UTR	Exon 9 of 9	NP_008968.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS8	ENST00000257359.7	TSL:1 MANE Select	c.*107C>G		3_prime_UTR	Exon 9 of 9	ENSP00000257359.6
	ADAMTS8	ENST00000531752.1	TSL:2	n.1724C>G		non_coding_transcript_exon	Exon 4 of 4
	ZBTB44-DT	ENST00000777858.1		n.320+11652G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152088 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000290 AC: 39 AN: 1346254 Hom.: 0 Cov.: 30 AF XY: 0.0000334 AC XY: 22 AN XY: 658848

African (AFR) AF: 0.00 AC: 0 AN: 30066

American (AMR) AF: 0.00 AC: 0 AN: 28684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19846

East Asian (EAS) AF: 0.00 AC: 0 AN: 38692

South Asian (SAS) AF: 0.00 AC: 0 AN: 69128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36762

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3686

European-Non Finnish (NFE) AF: 0.0000357 AC: 38 AN: 1063678

Other (OTH) AF: 0.0000179 AC: 1 AN: 55712

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152088 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74270

African (AFR) AF: 0.0000242 AC: 1 AN: 41400

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00 Hom.: 3037

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.38
DANN	Benign	0.53
PhyloP100		0.13

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: rs2242312; hg19: chr11-130275346;