chr7-130293242-T-C

Variant names:

• chr7-130293242-T-C
• rs1476324461
• NM_016352.4:c.62T>C

Variant summary

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

The NM_016352.4(CPA4):​c.62T>C​(p.Phe21Ser) 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. F21C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPA4 NM_016352.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.862

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.62T>C	p.Phe21Ser	missense	Exon 1 of 11	NP_057436.2	A4D1M3
	CPA4	NM_001163446.2		c.62T>C	p.Phe21Ser	missense	Exon 1 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.62T>C	p.Phe21Ser	missense	Exon 1 of 11	ENSP00000222482.4	Q9UI42-1
	CPA4	ENST00000474254.5	TSL:1	n.82T>C		non_coding_transcript_exon	Exon 1 of 7
	CPA4	ENST00000445470.6	TSL:2	c.62T>C	p.Phe21Ser	missense	Exon 1 of 10	ENSP00000412947.2	Q9UI42-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 250204 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.054
Eigen_PC	Benign	-0.035
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.082	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		2.5
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.011	D
Polyphen		0.53	P
Vest4		0.76
MutPred		0.77		Gain of disorder (P = 0.0045)
MVP		0.78
MPC		0.28
ClinPred		0.99	D
GERP RS		4.2
PromoterAI		0.089	Neutral
Varity_R		0.96
gMVP		0.74
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs1476324461; hg19: chr7-129933082;