rs61751103

chr15-58665172-C-Achr15-58665172-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_001110.4(ADAM10):c.510G>T(p.Gln170His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ADAM10 NM_001110.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.639

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, ADAM10
• BP4: Computational evidence support a benign effect (MetaRNN=0.29941672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM10	NM_001110.4	c.510G>T	p.Gln170His	missense_variant	5/16	ENST00000260408.8
ADAM10	NM_001320570.2	c.510G>T	p.Gln170His	missense_variant	5/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM10	ENST00000260408.8	c.510G>T	p.Gln170His	missense_variant	5/16	1	NM_001110.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
Cadd	Benign	17
Dann	Uncertain	0.99
DEOGEN2	Benign	0.19	T;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.92	D;T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.0	M;.
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.51	N;N
REVEL	Benign	0.23
Sift	Benign	0.19	T;D
Sift4G	Benign	0.14	T;.
Polyphen		0.0010	B;.
Vest4		0.57
MutPred		0.69		Gain of disorder (P = 0.0806);.;
MVP		0.98
MPC		0.29
ClinPred		0.56	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.053
gMVP		0.50

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

Other links and lift over

dbSNP: rs61751103; hg19: chr15-58957371;