NM_145004.7:c.826C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

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

Scores

3
8
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.123
Variant links:
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]

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ACMG classification

Classification made for transcript

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
ADAM32NM_145004.7 linkc.826C>G p.Leu276Val missense_variant Exon 9 of 25 ENST00000379907.9 NP_659441.4 Q8TC27A0A140VJD9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADAM32ENST00000379907.9 linkc.826C>G p.Leu276Val missense_variant Exon 9 of 25 1 NM_145004.7 ENSP00000369238.4 Q8TC27
ADAM32ENST00000519315.5 linkc.826C>G p.Leu276Val missense_variant Exon 9 of 19 1 ENSP00000429422.1 E7ER82
ADAM32ENST00000437682.6 linkc.847C>G p.Leu283Val missense_variant Exon 8 of 22 2 ENSP00000405978.2 E7EPX8
ADAM32ENST00000518259.1 linkn.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

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

Other links and lift over

dbSNP: rs373210270; hg19: chr8-39022708; API