9-18574183-G-C

Variant names:

• chr9-18574183-G-C
• rs78291060
• NM_001040272.6:c.391G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040272.6(ADAMTSL1):​c.391G>C​(p.Val131Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 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: 0.995

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13624495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL1	NM_001040272.6	c.391G>C	p.Val131Leu	missense_variant	Exon 4 of 29	ENST00000380548.9	NP_001035362.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL1	ENST00000380548.9	c.391G>C	p.Val131Leu	missense_variant	Exon 4 of 29	5	NM_001040272.6	ENSP00000369921.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T;.;.;.;.;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.14	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;M;.;.;M;M
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.3	N;N;N;N;N;N
REVEL	Benign	0.079
Sift	Uncertain	0.0060	D;T;T;T;T;T
Sift4G	Uncertain	0.012	D;D;D;T;D;T
Polyphen		0.016	B;.;.;.;B;.
Vest4		0.36
MutPred		0.41		Loss of ubiquitination at K126 (P = 0.1343);Loss of ubiquitination at K126 (P = 0.1343);Loss of ubiquitination at K126 (P = 0.1343);Loss of ubiquitination at K126 (P = 0.1343);Loss of ubiquitination at K126 (P = 0.1343);Loss of ubiquitination at K126 (P = 0.1343);
MVP		0.50
MPC		0.075
ClinPred		0.33	T
GERP RS		1.2
Varity_R		0.11
gMVP		0.32

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: rs78291060; hg19: chr9-18574181;