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GeneBe

9-18533259-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001040272.6(ADAMTSL1):c.204A>G(p.Gly68=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00229 in 1,606,928 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 51 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 30 hom. )

Consequence

ADAMTSL1
NM_001040272.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.44
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-18533259-A-G is Benign according to our data. Variant chr9-18533259-A-G is described in ClinVar as [Benign]. Clinvar id is 771427.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.44 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0127 (1941/152242) while in subpopulation AFR AF= 0.0444 (1845/41558). AF 95% confidence interval is 0.0427. There are 51 homozygotes in gnomad4. There are 915 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 51 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADAMTSL1NM_001040272.6 linkuse as main transcriptc.204A>G p.Gly68= synonymous_variant 3/29 ENST00000380548.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADAMTSL1ENST00000380548.9 linkuse as main transcriptc.204A>G p.Gly68= synonymous_variant 3/295 NM_001040272.6 P1Q8N6G6-3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0128
AC:
1942
AN:
152124
Hom.:
51
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0445
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00432
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000622
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00813
GnomAD3 exomes
AF:
0.00303
AC:
745
AN:
246250
Hom.:
17
AF XY:
0.00224
AC XY:
298
AN XY:
133232
show subpopulations
Gnomad AFR exome
AF:
0.0424
Gnomad AMR exome
AF:
0.00148
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000672
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000625
Gnomad OTH exome
AF:
0.00151
GnomAD4 exome
AF:
0.00120
AC:
1742
AN:
1454686
Hom.:
30
Cov.:
29
AF XY:
0.00107
AC XY:
772
AN XY:
723738
show subpopulations
Gnomad4 AFR exome
AF:
0.0421
Gnomad4 AMR exome
AF:
0.00184
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000106
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000487
Gnomad4 OTH exome
AF:
0.00322
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0127
AC:
1941
AN:
152242
Hom.:
51
Cov.:
32
AF XY:
0.0123
AC XY:
915
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.0444
Gnomad4 AMR
AF:
0.00432
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000622
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00805
Alfa
AF:
0.00233
Hom.:
3
Bravo
AF:
0.0141
Asia WGS
AF:
0.000868
AC:
3
AN:
3470

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
Cadd
Benign
14
Dann
Benign
0.76

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: rs16936832; hg19: chr9-18533257; API