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GeneBe

15-58599707-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001110.4(ADAM10):c.2043A>G(p.Val681=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000231 in 1,612,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

ADAM10
NM_001110.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.226
Variant links:
Genes affected
ADAM10 (HGNC:188): (ADAM metallopeptidase domain 10) Members of the ADAM family are cell surface proteins with a unique structure possessing both potential adhesion and protease domains. This gene encodes and ADAM family member that cleaves many proteins including TNF-alpha and E-cadherin. Alternate splicing results in multiple transcript variants encoding different proteins that may undergo similar processing. [provided by RefSeq, Feb 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 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=-0.62).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-58599707-T-C is Benign according to our data. Variant chr15-58599707-T-C is described in ClinVar as [Benign]. Clinvar id is 3045168.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=-0.226 with no splicing effect.
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 AC in GnomAd at 52 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADAM10NM_001110.4 linkuse as main transcriptc.2043A>G p.Val681= synonymous_variant 15/16 ENST00000260408.8
ADAM10NM_001320570.2 linkuse as main transcriptc.1950A>G p.Val650= synonymous_variant 14/15

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADAM10ENST00000260408.8 linkuse as main transcriptc.2043A>G p.Val681= synonymous_variant 15/161 NM_001110.4 P1O14672-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000344
AC:
52
AN:
151088
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000512
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000661
Gnomad ASJ
AF:
0.00634
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000430
AC:
108
AN:
251202
Hom.:
0
AF XY:
0.000390
AC XY:
53
AN XY:
135782
show subpopulations
Gnomad AFR exome
AF:
0.00105
Gnomad AMR exome
AF:
0.000578
Gnomad ASJ exome
AF:
0.00546
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000106
Gnomad OTH exome
AF:
0.000653
GnomAD4 exome
AF:
0.000220
AC:
321
AN:
1461034
Hom.:
0
Cov.:
30
AF XY:
0.000228
AC XY:
166
AN XY:
726866
show subpopulations
Gnomad4 AFR exome
AF:
0.00126
Gnomad4 AMR exome
AF:
0.000604
Gnomad4 ASJ exome
AF:
0.00582
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000576
Gnomad4 OTH exome
AF:
0.000580
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000344
AC:
52
AN:
151088
Hom.:
0
Cov.:
31
AF XY:
0.000353
AC XY:
26
AN XY:
73658
show subpopulations
Gnomad4 AFR
AF:
0.000512
Gnomad4 AMR
AF:
0.0000661
Gnomad4 ASJ
AF:
0.00634
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000838
Hom.:
0
Bravo
AF:
0.000499
EpiCase
AF:
0.000218
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

ADAM10-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 28, 2019This variant is classified as 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
BayesDel_noAF
Benign
-0.62
Cadd
Benign
5.6
Dann
Benign
0.82
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs144826830; hg19: chr15-58891906; API