NM_003812.4:c.933+3595G>A

Variant names:

• chr2-206553755-G-A
• rs10490515
• NM_003812.4:c.933+3595G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003812.4(ADAM23):​c.933+3595G>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADAM23 NM_003812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• Publications: 1 publications found

Genes affected

ADAM23 (HGNC:202): (ADAM metallopeptidase domain 23) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. It is reported that inactivation of this gene is associated with tumorigenesis in human cancers. [provided by RefSeq, May 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003812.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM23	NM_003812.4	MANE Select	c.933+3595G>A		intron	N/A	NP_003803.1
	ADAM23	NM_001410985.1		c.933+3595G>A		intron	N/A	NP_001397914.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM23	ENST00000264377.8	TSL:1 MANE Select	c.933+3595G>A		intron	N/A	ENSP00000264377.3
	ADAM23	ENST00000374415.7	TSL:5	c.933+3595G>A		intron	N/A	ENSP00000363536.3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.38
PhyloP100		0.30

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: rs10490515; hg19: chr2-207418479;