9-18504844-C-A

Variant names:

• chr9-18504844-C-A
• rs780536559
• NM_001040272.6:c.79C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001040272.6(ADAMTSL1):​c.79C>A​(p.Arg27Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADAMTSL1 NM_001040272.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.67

Genes affected

ADAMTSL1 (HGNC:14632): (ADAMTS like 1) This gene encodes a secreted protein and member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) family. This protein lacks the metalloproteinase and disintegrin-like domains, which are typical of the ADAMTS family, but contains other ADAMTS domains, including the thrombospondin type 1 motif. This protein may have important functions in the extracellular matrix. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL1	NM_001040272.6	c.79C>A	p.Arg27Ser	missense_variant	Exon 2 of 29	ENST00000380548.9	NP_001035362.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL1	ENST00000380548.9	c.79C>A	p.Arg27Ser	missense_variant	Exon 2 of 29	5	NM_001040272.6	ENSP00000369921.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	.;T;.;.;.;.;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D;D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.46	T;T;T;T;T;T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	2.0	.;M;M;.;.;M;M
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.6	.;D;N;N;N;N;N
REVEL	Benign	0.24
Sift	Uncertain	0.0020	.;D;D;T;T;D;D
Sift4G	Uncertain	0.015	.;D;T;T;T;T;D
Polyphen		1.0, 1.0	.;D;.;.;.;D;.
Vest4		0.57, 0.76, 0.74, 0.73, 0.74, 0.75
MutPred		0.33		.;Gain of phosphorylation at R27 (P = 0.012);Gain of phosphorylation at R27 (P = 0.012);Gain of phosphorylation at R27 (P = 0.012);Gain of phosphorylation at R27 (P = 0.012);Gain of phosphorylation at R27 (P = 0.012);Gain of phosphorylation at R27 (P = 0.012);
MVP		0.76
MPC		0.42
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.39
gMVP		0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs780536559; hg19: chr9-18504842;