Variant 9-18574040-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001040272.6(ADAMTSL1):c.248C>T(p.Pro83Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000157 in 1,461,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ADAMTSL1
NM_001040272.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.98

Variant links:

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]

ADAMTSL1 links:

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ACMG classification

Classification made for transcript

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=0.14756739).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTSL1	NM_001040272.6 linkuse as main transcript	c.248C>T	p.Pro83Leu	missense_variant	4/29	ENST00000380548.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTSL1	ENST00000380548.9 linkuse as main transcript	c.248C>T	p.Pro83Leu	missense_variant	4/29	5	NM_001040272.6	P1	Q8N6G6-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000359

AC:

AN:

250808

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135550

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461152

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726782

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000451

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2022

The c.248C>T (p.P83L) alteration is located in exon 4 (coding exon 4) of the ADAMTSL1 gene. This alteration results from a C to T substitution at nucleotide position 248, causing the proline (P) at amino acid position 83 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.15

T;.;.;.;.;.

Eigen

Benign

-0.021

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

D;D;D;D;D;D

M_CAP

Benign

0.0097

MetaRNN

Benign

0.15

T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.80

N;N;.;.;N;N

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.2

D;D;D;D;D;D

REVEL

Benign

0.14

Sift

Benign

0.077

T;T;T;T;T;T

Sift4G

Benign

0.24

T;T;T;T;T;T

Polyphen

0.13

B;.;.;.;B;.

Vest4

0.43

MutPred

0.46

Gain of stability (P = 0.0121);Gain of stability (P = 0.0121);Gain of stability (P = 0.0121);Gain of stability (P = 0.0121);Gain of stability (P = 0.0121);Gain of stability (P = 0.0121);

MVP

0.39

MPC

0.070

ClinPred

0.086

GERP RS

5.5

Varity_R

0.15

gMVP

0.28

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over