NM_001110.4:c.510G>T

Variant names:

• chr15-58665172-C-A
• rs61751103
• NM_001110.4:c.510G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 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 the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ADAM10 NM_001110.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.639
• Publications: 37 publications found

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]

ADAM10 Gene-Disease associations (from GenCC):

• reticulate acropigmentation of Kitamura

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29941672).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001110.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM10	NM_001110.4	MANE Select	c.510G>T	p.Gln170His	missense	Exon 5 of 16	NP_001101.1	O14672-1
	ADAM10	NM_001320570.2		c.510G>T	p.Gln170His	missense	Exon 5 of 15	NP_001307499.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM10	ENST00000260408.8	TSL:1 MANE Select	c.510G>T	p.Gln170His	missense	Exon 5 of 16	ENSP00000260408.3	O14672-1
	ADAM10	ENST00000402627.5	TSL:1	c.56-24342G>T		intron	N/A	ENSP00000386056.1	B5MC71
	ADAM10	ENST00000396136.6	TSL:1	n.*160G>T		non_coding_transcript_exon	Exon 3 of 14	ENSP00000456542.2	H3BS53

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.64
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.23
Sift	Benign	0.19	T
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

Other links and lift over

dbSNP: rs61751103; hg19: chr15-58957371;