Genetic Variant ADAMTSL1:p.Arg32Gln (chr9-18504860-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001040272.6(ADAMTSL1):c.95G>A(p.Arg32Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000154 in 1,613,910 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

ADAMTSL1
NM_001040272.6 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.65

Publications

2 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0100031495).

BP6

Variant 9-18504860-G-A is Benign according to our data. Variant chr9-18504860-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3054042.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040272.6. 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
	ADAMTSL1	NM_001040272.6	MANE Select	c.95G>A	p.Arg32Gln	missense	Exon 2 of 29	NP_001035362.3	Q8N6G6-3
	ADAMTSL1	NM_052866.5		c.95G>A	p.Arg32Gln	missense	Exon 2 of 13	NP_443098.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAMTSL1	ENST00000380548.9	TSL:5 MANE Select	c.95G>A	p.Arg32Gln	missense	Exon 2 of 29	ENSP00000369921.4	Q8N6G6-3
ADAMTSL1	ENST00000327883.11	TSL:1	c.95G>A	p.Arg32Gln	missense	Exon 2 of 13	ENSP00000327887.7	Q8N6G6-1
ADAMTSL1	ENST00000380566.8	TSL:1	c.95G>A	p.Arg32Gln	missense	Exon 2 of 10	ENSP00000369940.4	Q8N6G6-2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000562

AC:

141

AN:

251010

AF XY:

0.000457

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00388

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000159

AC:

232

AN:

1461704

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

107

AN XY:

727156

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33466

American (AMR)

AF:

0.00349

AC:

156

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.000126

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53354

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000531

AC:

AN:

1111964

Other (OTH)

AF:

0.000166

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000105

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41464

American (AMR)

AF:

0.000851

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000265

Hom.:

Bravo

AF:

0.000246

ExAC

AF:

0.000338

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ADAMTSL1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.17

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.38

M_CAP

Benign

0.030

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

5.7

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.98

REVEL

Benign

0.086

Sift

Benign

0.039

Sift4G

Uncertain

0.030

Polyphen

0.0020

Vest4

0.31

MVP

0.56

MPC

0.11

ClinPred

0.097

GERP RS

3.4

Varity_R

0.045

gMVP

0.30

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over