rs558004630

Variant names:

• chr19-16893308-T-A
• rs558004630
• NM_015692.5:c.5458A>T

Your query was ambiguous. Multiple possible variants found:

• chr19-16893308-T-A
• chr19-16893308-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015692.5(CPAMD8):​c.5458A>T​(p.Ser1820Cys) 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. 13/17 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. S1820G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CPAMD8 NM_015692.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• anterior segment dysgenesis 8

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053817064).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015692.5. 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
	CPAMD8	NM_015692.5	MANE Select	c.5458A>T	p.Ser1820Cys	missense	Exon 42 of 42	NP_056507.3	Q8IZJ3-1
	CPAMD8	NR_147452.2		n.1368A>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPAMD8	ENST00000443236.7	TSL:1 MANE Select	c.5458A>T	p.Ser1820Cys	missense	Exon 42 of 42	ENSP00000402505.3	Q8IZJ3-1
	CPAMD8	ENST00000942844.1		c.5422A>T	p.Ser1808Cys	missense	Exon 42 of 42	ENSP00000612903.1
	CPAMD8	ENST00000651564.2		c.*1108A>T		3_prime_UTR	Exon 42 of 42	ENSP00000498697.2	Q8IZJ3-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	2.4
DANN	Benign	0.81
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.1	T
PhyloP100		-1.2
PrimateAI	Benign	0.44	T
Sift4G	Pathogenic	0.0	D
Vest4		0.13
MVP		0.055
MPC		0.068
ClinPred		0.062	T
GERP RS		-2.6
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs558004630; hg19: chr19-17004119;