NM_145004.7:c.644A>T

Variant names:

• chr8-39164813-A-T
• rs1804725755
• NM_145004.7:c.644A>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_145004.7(ADAM32):​c.644A>T​(p.Glu215Val) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADAM32 NM_145004.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.54
• Publications: 0 publications found

Genes affected

ADAM32 (HGNC:15479): (ADAM metallopeptidase domain 32) This gene encodes a member of the disintegrin family of membrane-anchored proteins that play a role in diverse biological processes such as brain development, fertilization, tumor development and inflammation. This gene is predominantly expressed in the testis. The encoded protein undergoes proteolytic processing to generate a mature polypeptide comprised of an metalloprotease, disintegrin and epidermal growth factor-like domains. This gene is located in a cluster of other disintegrin and metallopeptidase family genes on chromosome 8. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.866

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145004.7. 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
	ADAM32	NM_145004.7	MANE Select	c.644A>T	p.Glu215Val	missense	Exon 8 of 25	NP_659441.4
	ADAM32	NM_001313994.1		c.665A>T	p.Glu222Val	missense	Exon 7 of 22	NP_001300923.1	Q8TC27

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM32	ENST00000379907.9	TSL:1 MANE Select	c.644A>T	p.Glu215Val	missense	Exon 8 of 25	ENSP00000369238.4	Q8TC27
	ADAM32	ENST00000519315.5	TSL:1	c.644A>T	p.Glu215Val	missense	Exon 8 of 19	ENSP00000429422.1	E7ER82
	ADAM32	ENST00000864644.1		c.644A>T	p.Glu215Val	missense	Exon 8 of 24	ENSP00000534703.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	Uncertain	0.49
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.094
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.057	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	-0.018	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		2.5
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.048	D
Polyphen		0.80	P
Vest4		0.57
MutPred		0.74		Gain of methylation at K212 (P = 0.045)
MVP		0.71
MPC		0.35
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.45
gMVP		0.43
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.20		Position offset: 22

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

Other links and lift over

dbSNP: rs1804725755; hg19: chr8-39022332;