chr9-18622276-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001040272.6(ADAMTSL1):​c.508G>A​(p.Val170Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00241 in 1,613,976 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0024 ( 9 hom. )

Consequence

ADAMTSL1
NM_001040272.6 missense

Scores

2
17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.87
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0058428645).
BP6
Variant 9-18622276-G-A is Benign according to our data. Variant chr9-18622276-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3042672.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADAMTSL1NM_001040272.6 linkuse as main transcriptc.508G>A p.Val170Ile missense_variant 5/29 ENST00000380548.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADAMTSL1ENST00000380548.9 linkuse as main transcriptc.508G>A p.Val170Ile missense_variant 5/295 NM_001040272.6 P1Q8N6G6-3

Frequencies

GnomAD3 genomes
AF:
0.00218
AC:
331
AN:
152144
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000362
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00282
Gnomad ASJ
AF:
0.000864
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00476
Gnomad FIN
AF:
0.00217
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.00315
Gnomad OTH
AF:
0.00192
GnomAD3 exomes
AF:
0.00262
AC:
657
AN:
250822
Hom.:
0
AF XY:
0.00291
AC XY:
395
AN XY:
135512
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.00255
Gnomad ASJ exome
AF:
0.000795
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00474
Gnomad FIN exome
AF:
0.00180
Gnomad NFE exome
AF:
0.00316
Gnomad OTH exome
AF:
0.00229
GnomAD4 exome
AF:
0.00243
AC:
3555
AN:
1461714
Hom.:
9
Cov.:
31
AF XY:
0.00259
AC XY:
1885
AN XY:
727154
show subpopulations
Gnomad4 AFR exome
AF:
0.000359
Gnomad4 AMR exome
AF:
0.00253
Gnomad4 ASJ exome
AF:
0.000727
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00505
Gnomad4 FIN exome
AF:
0.00178
Gnomad4 NFE exome
AF:
0.00240
Gnomad4 OTH exome
AF:
0.00233
GnomAD4 genome
AF:
0.00217
AC:
331
AN:
152262
Hom.:
1
Cov.:
32
AF XY:
0.00228
AC XY:
170
AN XY:
74434
show subpopulations
Gnomad4 AFR
AF:
0.000361
Gnomad4 AMR
AF:
0.00281
Gnomad4 ASJ
AF:
0.000864
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00477
Gnomad4 FIN
AF:
0.00217
Gnomad4 NFE
AF:
0.00315
Gnomad4 OTH
AF:
0.00190
Alfa
AF:
0.00298
Hom.:
3
Bravo
AF:
0.00204
TwinsUK
AF:
0.00189
AC:
7
ALSPAC
AF:
0.00285
AC:
11
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.00291
AC:
25
ExAC
AF:
0.00293
AC:
356
Asia WGS
AF:
0.00231
AC:
8
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

ADAMTSL1-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMay 25, 2022This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.083
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.036
T;.;.;.;.
Eigen
Benign
-0.25
Eigen_PC
Benign
-0.089
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.79
T;T;T;T;T
M_CAP
Benign
0.0056
T
MetaRNN
Benign
0.0058
T;T;T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.1
L;L;.;L;L
MutationTaster
Benign
0.98
N;N;N;N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.72
N;N;N;N;N
REVEL
Benign
0.092
Sift
Benign
0.12
T;T;T;T;T
Sift4G
Benign
0.083
T;T;T;T;T
Polyphen
0.0010
B;.;.;B;.
Vest4
0.17
MVP
0.46
MPC
0.056
ClinPred
0.020
T
GERP RS
2.7
Varity_R
0.043
gMVP
0.16

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.

Other links and lift over

dbSNP: rs146511703; hg19: chr9-18622274; COSMIC: COSV104586201; API