chr8-24482244-C-T

Variant names:

• chr8-24482244-C-T
• rs777987045
• NM_003817.4:c.808C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003817.4(ADAM7):​c.808C>T​(p.Arg270Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000292 in 1,610,792 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: ADAM7 NM_003817.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.401
• Publications: 2 publications found

Genes affected

ADAM7 (HGNC:214): (ADAM metallopeptidase domain 7) This gene encodes a member of the ADAMs family of zinc proteases. These transmembrane proteins play roles in multiple processes including cell signaling, adhesion and migration. The encoded protein lacks protease activity and may play roles in protein-protein interactions and cell adhesion processes including sperm-egg fusion. Mutations in this gene may be involved in the progression of melanoma. [provided by RefSeq, Oct 2011]

ADAM7-AS1 (HGNC:56152): (ADAM7, ADAMDEC1 and ADAM28 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003817.4. 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
	ADAM7	NM_003817.4	MANE Select	c.808C>T	p.Arg270Cys	missense	Exon 9 of 22	NP_003808.2	A0A384MTL6
	ADAM7-AS1	NR_125808.1		n.79+66296G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM7	ENST00000175238.10	TSL:1 MANE Select	c.808C>T	p.Arg270Cys	missense	Exon 9 of 22	ENSP00000175238.5	Q9H2U9-1
	ADAM7	ENST00000520720.1	TSL:1	c.124C>T	p.Arg42Cys	missense	Exon 3 of 15	ENSP00000430400.1	E5RK87
	ADAM7	ENST00000380789.5	TSL:5	c.808C>T	p.Arg270Cys	missense	Exon 9 of 23	ENSP00000370166.1	C9JK28

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151962 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000765 AC: 19 AN: 248494 AF XY: 0.0000895

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000295 AC: 43 AN: 1458830 Hom.: 0 Cov.: 32 AF XY: 0.0000276 AC XY: 20 AN XY: 725480

African (AFR) AF: 0.0000601 AC: 2 AN: 33292

American (AMR) AF: 0.00 AC: 0 AN: 44266

Ashkenazi Jewish (ASJ) AF: 0.0000767 AC: 2 AN: 26062

East Asian (EAS) AF: 0.00 AC: 0 AN: 39552

South Asian (SAS) AF: 0.00 AC: 0 AN: 85262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5738

European-Non Finnish (NFE) AF: 0.0000342 AC: 38 AN: 1110982

Other (OTH) AF: 0.00 AC: 0 AN: 60302

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151962 Hom.: 0 Cov.: 33 AF XY: 0.0000270 AC XY: 2 AN XY: 74196

African (AFR) AF: 0.0000242 AC: 1 AN: 41354

American (AMR) AF: 0.00 AC: 0 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.000124 AC: 15

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.081	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		0.40
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.19
Sift	Benign	0.13	T
Sift4G	Benign	0.12	T
Polyphen		0.96	D
Vest4		0.42
MutPred		0.72		Loss of MoRF binding (P = 0.0338)
MVP		0.80
MPC		0.28
ClinPred		0.65	D
GERP RS		2.2
Varity_R		0.28
gMVP		0.38
Mutation Taster		=98/2	polymorphism

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: rs777987045; hg19: chr8-24339757;