rs201616533

Variant names:

• chr8-39136667-C-A
• NM_145004.7:c.149C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-39136667-C-A
• chr8-39136667-C-G

Variant summary

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

The NM_145004.7(ADAM32):​c.149C>A​(p.Ser50Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,386,484 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: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ADAM32 NM_145004.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.23

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 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
ADAM32	NM_145004.7	c.149C>A	p.Ser50Tyr	missense_variant	Exon 3 of 25	ENST00000379907.9	NP_659441.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM32	ENST00000379907.9	c.149C>A	p.Ser50Tyr	missense_variant	Exon 3 of 25	1	NM_145004.7	ENSP00000369238.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.21e-7 AC: 1 AN: 1386484 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 688278

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000324

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	.;.;T;.;T;.
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.77	T;T;T;T;T;T
M_CAP	Benign	0.0050	T
MetaRNN	Uncertain	0.65	D;D;D;D;D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.7	.;.;.;.;M;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.7	D;D;D;D;D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D;D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D;D
Polyphen		0.98, 1.0	.;.;D;D;D;.
Vest4		0.75, 0.77, 0.75
MutPred		0.56		.;Loss of disorder (P = 0.0416);.;Loss of disorder (P = 0.0416);Loss of disorder (P = 0.0416);Loss of disorder (P = 0.0416);
MVP		0.38
MPC		0.37
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.51
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-38994186;