8-67517949-GA-CG

Variant names:

• chr8-67517949-GA-CG
• NM_020361.5:c.290_291delTCinsCG
• CPA6 p.Phe97Ser

Variant summary

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

The NM_020361.5(CPA6):​c.290_291delTCinsCG​(p.Phe97Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F97L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPA6 NM_020361.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.76
• Publications: 0 publications found

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]

CPA6 Gene-Disease associations (from GenCC):

• benign familial mesial temporal lobe epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial mesial temporal lobe epilepsy with febrile seizures

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial temporal lobe epilepsy 5

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• febrile seizures, familial, 11

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• epilepsy

  Inheritance: AD, AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020361.5. 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
	CPA6	NM_020361.5	MANE Select	c.290_291delTCinsCG	p.Phe97Ser	missense	N/A	NP_065094.3
	CPA6	NM_001440615.1		c.290_291delTCinsCG	p.Phe97Ser	missense	N/A	NP_001427544.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPA6	ENST00000297770.10	TSL:1 MANE Select	c.290_291delTCinsCG	p.Phe97Ser	missense	N/A	ENSP00000297770.4	Q8N4T0-1
	CPA6	ENST00000518549.1	TSL:1	n.504_505delTCinsCG		non_coding_transcript_exon	Exon 3 of 8
	CPA6	ENST00000479862.6	TSL:1	n.193-6295_193-6294delTCinsCG		intron	N/A	ENSP00000419016.2	Q8N4T0-3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.8

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-68430184;