8-24499305-A-T

Position:

• chr8-24499305-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003817.4(ADAM7):​c.1912A>T​(p.Asn638Tyr) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N638H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADAM7 NM_003817.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

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:):

ACMG classification

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=0.109894514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM7	NM_003817.4	c.1912A>T	p.Asn638Tyr	missense_variant	17/22	ENST00000175238.10	NP_003808.2
ADAM7-AS1	NR_125808.1	n.79+49235T>A		intron_variant
ADAM7-AS2	NR_125809.1	n.447-7145T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM7	ENST00000175238.10	c.1912A>T	p.Asn638Tyr	missense_variant	17/22	1	NM_003817.4	ENSP00000175238.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	3.6
DANN	Benign	0.65
DEOGEN2	Benign	0.091	T;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.085	T;T;T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Pathogenic	3.1	M;.;.
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.6	D;D;N
REVEL	Benign	0.065
Sift	Benign	0.046	D;T;D
Sift4G	Uncertain	0.039	D;D;D
Polyphen		0.097	B;.;B
Vest4		0.20
MutPred		0.38		Loss of disorder (P = 0.0231);Loss of disorder (P = 0.0231);.;
MVP		0.31
MPC		0.077
ClinPred		0.18	T
GERP RS		-4.4
Varity_R		0.038
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs13259668; hg19: chr8-24356818;