19-16896213-C-T

Position:

• chr19-16896213-C-T

Variant summary

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

The NM_015692.5(CPAMD8):​c.5389G>A​(p.Asp1797Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CPAMD8 NM_015692.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.714

Genes affected

CPAMD8 (HGNC:23228): (C3 and PZP like alpha-2-macroglobulin domain containing 8) This gene encodes a member of the protease inhibitor I39 (alpha-2-macroglobulin) family of proteins. These proteins are important in innate and acquired immunity. The encoded protein is membrane-associated and proteolytically processed to generate two chains. Mutations in this gene cause a form of anterior segment dysgenesis, a developmental disorder of the eye. [provided by RefSeq, May 2017]

CPAMD8 (HGNC:):

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=0.09838566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPAMD8	NM_015692.5	c.5389G>A	p.Asp1797Asn	missense_variant	41/42	ENST00000443236.7	NP_056507.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPAMD8	ENST00000443236.7	c.5389G>A	p.Asp1797Asn	missense_variant	41/42	1	NM_015692.5	ENSP00000402505.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461644 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727136

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 24, 2024

The c.5530G>A (p.D1844N) alteration is located in exon 41 (coding exon 41) of the CPAMD8 gene. This alteration results from a G to A substitution at nucleotide position 5530, causing the aspartic acid (D) at amino acid position 1844 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.71	T
Sift4G	Uncertain	0.023	D
Vest4		0.33
MVP		0.28
MPC		0.37
ClinPred		0.32	T
GERP RS		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-17007024;