7-130367540-T-G

Variant names:

• chr7-130367540-T-G
• rs11761888
• NM_080385.5:c.1007T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080385.5(CPA5):​c.1007T>G​(p.Leu336Trp) 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 benign outcome for this variant. 15/21 in silico tools predict a benign 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. L336S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPA5 NM_080385.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

Genes affected

CPA5 (HGNC:15722): (carboxypeptidase A5) Carboxypeptidases have functions ranging from digestion of food to selective biosynthesis of neuroendocrine peptides. Members of the A/B subfamily of carboxypeptidases, such as CPA5, contain an approximately 90-amino acid pro region that assists in the folding of the active carboxypeptidase domain. Cleavage of the pro region activates the enzyme (Wei et al., 2002 [PubMed 11836249]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.173888).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPA5	NM_080385.5	c.1007T>G	p.Leu336Trp	missense_variant	Exon 11 of 13	ENST00000474905.6	NP_525124.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPA5	ENST00000474905.6	c.1007T>G	p.Leu336Trp	missense_variant	Exon 11 of 13	1	NM_080385.5	ENSP00000417314.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251464 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135908

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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.: 34

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	18
DANN	Benign	0.85
DEOGEN2	Benign	0.041	T;T;T;.;T;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.25	.;.;.;T;.;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	L;L;L;L;L;L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.2	N;N;N;N;N;N
REVEL	Benign	0.089
Sift	Uncertain	0.0010	D;D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D;D
Polyphen		0.67	P;P;P;.;P;P
Vest4		0.20
MutPred		0.56		Gain of catalytic residue at P339 (P = 0.0259);Gain of catalytic residue at P339 (P = 0.0259);Gain of catalytic residue at P339 (P = 0.0259);Gain of catalytic residue at P339 (P = 0.0259);Gain of catalytic residue at P339 (P = 0.0259);Gain of catalytic residue at P339 (P = 0.0259);
MVP		0.27
MPC		0.38
ClinPred		0.23	T
GERP RS		3.7
Varity_R		0.14
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11761888; hg19: chr7-130007381;