8-24472122-CAAAAAAAA-CAAAAAA

Variant names:

• chr8-24472122-CAA-C
• rs55708871
• NM_003817.4:c.633+3317_633+3318delAA

Variant summary

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

The NM_003817.4(ADAM7):​c.633+3317_633+3318delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 102,744 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0024 (0 hom., cov: 23)
• Consequence: ADAM7 NM_003817.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.682

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM7	NM_003817.4	c.633+3317_633+3318delAA		intron_variant	Intron 7 of 21	ENST00000175238.10	NP_003808.2
ADAM7-AS1	NR_125808.1	n.79+76416_79+76417delTT		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM7	ENST00000175238.10	c.633+3303_633+3304delAA		intron_variant	Intron 7 of 21	1	NM_003817.4	ENSP00000175238.5
ADAM7	ENST00000380789.5	c.633+3303_633+3304delAA		intron_variant	Intron 7 of 22	5		ENSP00000370166.1
ADAM7-AS1	ENST00000519689.1	n.185-84133_185-84132delTT		intron_variant	Intron 2 of 4	4
ADAM7-AS1	ENST00000523578.5	n.79+76416_79+76417delTT		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes AF: 0.00237 AC: 244 AN: 102752 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00686

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000742

Gnomad ASJ AF: 0.000407

Gnomad EAS AF: 0.000806

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000194

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000431

Gnomad OTH AF: 0.00208

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00238 AC: 245 AN: 102744 Hom.: 0 Cov.: 23 AF XY: 0.00241 AC XY: 118 AN XY: 49004

Gnomad4 AFR AF: 0.00688

Gnomad4 AMR AF: 0.000742

Gnomad4 ASJ AF: 0.000407

Gnomad4 EAS AF: 0.000808

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000194

Gnomad4 NFE AF: 0.000431

Gnomad4 OTH AF: 0.00207

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs55708871; hg19: chr8-24329635;