Variant 1-155054444-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_207197.3(ADAM15):c.550C>T(p.Arg184Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,460,910 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

ADAM15
NM_207197.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.243

Variant links:

Genes affected

ADAM15 (HGNC:193): (ADAM metallopeptidase domain 15) The protein encoded by this gene is a member of the ADAM (a disintegrin and metalloproteinase) protein family. ADAM family members are type I transmembrane glycoproteins known to be involved in cell adhesion and proteolytic ectodomain processing of cytokines and adhesion molecules. This protein contains multiple functional domains including a zinc-binding metalloprotease domain, a disintegrin-like domain, as well as a EGF-like domain. Through its disintegrin-like domain, this protein specifically interacts with the integrin beta chain, beta 3. It also interacts with Src family protein-tyrosine kinases in a phosphorylation-dependent manner, suggesting that this protein may function in cell-cell adhesion as well as in cellular signaling. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

ADAM15 links:

ADAM15-EFNA4 (HGNC:):

ADAM15-EFNA4 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=0.108692795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADAM15	NM_207197.3 linkuse as main transcript	c.550C>T	p.Arg184Trp	missense_variant	6/23	ENST00000356955.7	NP_997080.1
ADAM15-EFNA4	NR_176418.1 linkuse as main transcript	n.621C>T		non_coding_transcript_exon_variant	6/26
DCST1-AS1	NR_040773.1 linkuse as main transcript	n.236-5083G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM15	ENST00000356955.7 linkuse as main transcript	c.550C>T	p.Arg184Trp	missense_variant	6/23	1	NM_207197.3	ENSP00000349436	A2	Q13444-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1460910

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726668

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000673

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

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

Sep 01, 2021

The c.550C>T (p.R184W) alteration is located in exon 6 (coding exon 6) of the ADAM15 gene. This alteration results from a C to T substitution at nucleotide position 550, causing the arginine (R) at amino acid position 184 to be replaced by a tryptophan (W). 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

0.076

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.26

T;.;.;.;.;.;.;.;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.19

T;T;T;T;T;T;T;T;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.11

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.4

L;L;L;L;L;L;L;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-2.1

N;N;N;N;N;N;N;N;.

REVEL

Benign

0.10

Sift

Benign

0.17

T;T;T;T;T;T;T;T;.

Sift4G

Uncertain

0.020

D;D;D;D;D;D;D;D;D

Polyphen

0.94

P;D;P;P;P;P;P;.;.

Vest4

0.18

MutPred

0.47

Loss of disorder (P = 0.0045);Loss of disorder (P = 0.0045);Loss of disorder (P = 0.0045);Loss of disorder (P = 0.0045);Loss of disorder (P = 0.0045);Loss of disorder (P = 0.0045);Loss of disorder (P = 0.0045);.;.;

MVP

0.26

MPC

0.48

ClinPred

0.38

GERP RS

-3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.041

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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