rs1554526426

Variant names:

• chr8-67624243-A-C
• NM_020361.5:c.125T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-67624243-A-C
• chr8-67624243-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020361.5(CPA6):​c.125T>G​(p.Val42Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000762 in 1,311,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: CPA6 NM_020361.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26

Genes affected

CPA6 (HGNC:17245): (carboxypeptidase A6) The gene encodes a member of the peptidase M14 family of metallocarboxypeptidases. The encoded preproprotein is proteolytically processed to generate the mature enzyme, which catalyzes the release of large hydrophobic C-terminal amino acids. This enzyme has functions ranging from digestion of food to selective biosynthesis of neuroendocrine peptides. Mutations in this gene may be linked to epilepsy and febrile seizures, and a translocation t(6;8)(q26;q13) involving this gene has been associated with Duane retraction syndrome. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.911

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPA6	NM_020361.5	c.125T>G	p.Val42Gly	missense_variant	Exon 2 of 11	ENST00000297770.10	NP_065094.3
CPA6	XM_017013647.2	c.125T>G	p.Val42Gly	missense_variant	Exon 2 of 7		XP_016869136.1
CPA6	XM_017013646.2	c.-195T>G		5_prime_UTR_variant	Exon 3 of 11		XP_016869135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPA6	ENST00000297770.10	c.125T>G	p.Val42Gly	missense_variant	Exon 2 of 11	1	NM_020361.5	ENSP00000297770.4
CPA6	ENST00000479862.6	n.125T>G		non_coding_transcript_exon_variant	Exon 2 of 8	1		ENSP00000419016.2
CPA6	ENST00000518549.1	n.339T>G		non_coding_transcript_exon_variant	Exon 2 of 8	1
CPA6	ENST00000638254.1	n.125T>G		non_coding_transcript_exon_variant	Exon 2 of 10	5		ENSP00000491129.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.62e-7 AC: 1 AN: 1311788 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 659878

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000102

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	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.060	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.55
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.79		Loss of stability (P = 0.0176);
MVP		0.81
MPC		0.20
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.94
gMVP		0.89

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-68536478;