Genetic Variant NM_003817.4:c.633+3316_633+3318dupAAA (chr8-24472122-C-CAAA) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_003817.4(ADAM7):c.633+3316_633+3318dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000973 in 102,770 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 0.0000097 ( 0 hom., cov: 23)

Consequence

ADAM7
NM_003817.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.386

Variant links:

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 links:

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

ADAM7-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 link	c.633+3316_633+3318dupAAA		intron_variant	Intron 7 of 21	ENST00000175238.10	NP_003808.2	Q9H2U9-1A0A384MTL6
ADAM7-AS1	NR_125808.1 link	n.79+76415_79+76417dupTTT		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADAM7	ENST00000175238.10 link	c.633+3302_633+3303insAAA	intron_variant	Intron 7 of 21	1	NM_003817.4	ENSP00000175238.5	Q9H2U9-1
ADAM7	ENST00000380789.5 link	c.633+3302_633+3303insAAA	intron_variant	Intron 7 of 22	5		ENSP00000370166.1	C9JK28
ADAM7-AS1	ENST00000519689.1 link	n.185-84132_185-84131insTTT	intron_variant	Intron 2 of 4	4
ADAM7-AS1	ENST00000523578.5 link	n.79+76417_79+76418insTTT	intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.00000973

AC:

AN:

102770

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000215

Gnomad OTH

AF:

0.00

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

GnomAD4 genome

AF:

0.00000973

AC:

AN:

102770

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

49006

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000215

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over