chr16-77283965-CCT-ACG

Variant names:

• chr16-77283965-CCT-ACG
• NM_199355.4:c.3655_3657delAGGinsCGT
• ADAMTS18 p.1220

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP7

The NM_199355.4(ADAMTS18):​c.3655_3657delAGGinsCGT​(p.1220) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R1219R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ADAMTS18 NM_199355.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.11
• Publications: 0 publications found

Genes affected

ADAMTS18 (HGNC:17110): (ADAM metallopeptidase with thrombospondin type 1 motif 18) 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 regulate hemostatic balance and function as a tumor suppressor. Mutations in this gene may be associated with microcornea, myopic chorioretinal atrophy, and telecanthus (MMCAT) and cone-rod dystrophy in human patients. [provided by RefSeq, May 2016]

ADAMTS18 Gene-Disease associations (from GenCC):

• microcornea-myopic chorioretinal atrophy

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P
• inherited retinal dystrophy

  Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

ENSG00000260922 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP7: Synonymous conserved (PhyloP=3.11 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199355.4. 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
	ADAMTS18	NM_199355.4	MANE Select	c.3655_3657delAGGinsCGT	p.1220	synonymous	N/A	NP_955387.1	Q8TE60-1
	ADAMTS18	NM_001326358.2		c.3139_3141delAGGinsCGT	p.1048	synonymous	N/A	NP_001313287.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS18	ENST00000282849.10	TSL:1 MANE Select	c.3655_3657delAGGinsCGT	p.1220	synonymous	N/A	ENSP00000282849.5	Q8TE60-1
	ADAMTS18	ENST00000562332.1	TSL:2	c.94+5297_94+5299delAGGinsCGT		intron	N/A	ENSP00000454368.1	H3BMG1
	ENSG00000260922	ENST00000561672.1	TSL:2	n.74-5311_74-5309delCCTinsACG		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-77317862;