NM_016352.4:c.283C>A

Variant names:

• chr7-130299402-C-A
• rs1341282367
• NM_016352.4:c.283C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016352.4(CPA4):​c.283C>A​(p.Gln95Lys) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPA4 NM_016352.4 missense, splice_region
• Scores: Splicing: ADA: 0.9252
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.23
• Publications: 0 publications found

Genes affected

CPA4 (HGNC:15740): (carboxypeptidase A4) This gene is a member of the carboxypeptidase A/B subfamily, and it is located in a cluster with three other family members on chromosome 7. Carboxypeptidases are zinc-containing exopeptidases that catalyze the release of carboxy-terminal amino acids, and are synthesized as zymogens that are activated by proteolytic cleavage. This gene could be involved in the histone hyperacetylation pathway. It is imprinted and may be a strong candidate gene for prostate cancer aggressiveness. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016352.4. 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
	CPA4	NM_016352.4	MANE Select	c.283C>A	p.Gln95Lys	missense splice_region	Exon 3 of 11	NP_057436.2	A4D1M3
	CPA4	NM_001163446.2		c.283C>A	p.Gln95Lys	missense splice_region	Exon 3 of 10	NP_001156918.1	Q9UI42-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPA4	ENST00000222482.10	TSL:1 MANE Select	c.283C>A	p.Gln95Lys	missense splice_region	Exon 3 of 11	ENSP00000222482.4	Q9UI42-1
	CPA4	ENST00000474254.5	TSL:1	n.303C>A		splice_region non_coding_transcript_exon	Exon 3 of 7
	CPA4	ENST00000445470.6	TSL:2	c.283C>A	p.Gln95Lys	missense splice_region	Exon 3 of 10	ENSP00000412947.2	Q9UI42-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Benign	0.33
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		5.2
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.65		Gain of ubiquitination at Q95 (P = 0.0177)
MVP		0.66
MPC		0.63
ClinPred		0.99	D
GERP RS		6.1
Varity_R		0.88
gMVP		0.83
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.93
dbscSNV1_RF	Pathogenic	0.79
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: rs1341282367; hg19: chr7-129939242;