NM_145004.7:c.826C>G

Variant names:

• chr8-39165189-C-G
• rs373210270
• NM_145004.7:c.826C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_145004.7(ADAM32):​c.826C>G​(p.Leu276Val) 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. 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. L276I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADAM32 NM_145004.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.83

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM32	NM_145004.7	c.826C>G	p.Leu276Val	missense_variant	Exon 9 of 25	ENST00000379907.9	NP_659441.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM32	ENST00000379907.9	c.826C>G	p.Leu276Val	missense_variant	Exon 9 of 25	1	NM_145004.7	ENSP00000369238.4
ADAM32	ENST00000519315.5	c.826C>G	p.Leu276Val	missense_variant	Exon 9 of 19	1		ENSP00000429422.1
ADAM32	ENST00000437682.6	c.847C>G	p.Leu283Val	missense_variant	Exon 8 of 22	2		ENSP00000405978.2
ADAM32	ENST00000518259.1	n.854C>G		non_coding_transcript_exon_variant	Exon 9 of 11	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ESP6500AA AF: 0.000277 AC: 1

ESP6500EA AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;.;T
Eigen	Uncertain	0.33
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.92	D;D;T
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Pathogenic	3.5	.;.;H
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Uncertain	0.49
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.66
MVP		0.77
MPC		0.34
ClinPred		0.99	D
GERP RS		1.6
Varity_R		0.48
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.24		Position offset: 7

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

Publications

LitVar

Other links and lift over

dbSNP: rs373210270; hg19: chr8-39022708;