NM_003817.4:c.1741C>A

Variant names:

• chr8-24493128-C-A
• rs777916485
• NM_003817.4:c.1741C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003817.4(ADAM7):​c.1741C>A​(p.Pro581Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 0.0000082 (0 hom.)
• Consequence: ADAM7 NM_003817.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.648
• Publications: 0 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-AS2 (HGNC:56153): (ADAM7 antisense RNA 2)

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10847911).

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.1741C>A	p.Pro581Thr	missense	Exon 16 of 22	NP_003808.2	A0A384MTL6
	ADAM7-AS1	NR_125808.1		n.79+55412G>T		intron	N/A
	ADAM7-AS2	NR_125809.1		n.447-968G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM7	ENST00000175238.10	TSL:1 MANE Select	c.1741C>A	p.Pro581Thr	missense	Exon 16 of 22	ENSP00000175238.5	Q9H2U9-1
	ADAM7	ENST00000520720.1	TSL:1	c.1057C>A	p.Pro353Thr	missense	Exon 10 of 15	ENSP00000430400.1	E5RK87
	ADAM7	ENST00000380789.5	TSL:5	c.1741C>A	p.Pro581Thr	missense	Exon 16 of 23	ENSP00000370166.1	C9JK28

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000800 AC: 2 AN: 250044 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461072 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 726840

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.00 AC: 0 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000990 AC: 11 AN: 1111574

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

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	0.078
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.93
DANN	Benign	0.95
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.65
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.038
Sift	Benign	0.12	T
Sift4G	Benign	0.30	T
Polyphen		0.67	P
Vest4		0.15
MutPred		0.49		Loss of methylation at K583 (P = 0.0785)
MVP		0.12
MPC		0.14
ClinPred		0.083	T
GERP RS		-4.5
Varity_R		0.046
gMVP		0.62
Mutation Taster		=91/9	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: rs777916485; hg19: chr8-24350641;