Genetic Variant CPAMD8:p.Ala1841Thr (chr19-16893245-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015692.5(CPAMD8):c.5521G>A(p.Ala1841Thr) 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. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CPAMD8
NM_015692.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.757

Publications

0 publications found

Variant links:

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)

CPAMD8 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15247369).

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.5521G>A	p.Ala1841Thr	missense	Exon 42 of 42	NP_056507.3	Q8IZJ3-1
	CPAMD8	NR_147452.2		n.1431G>A		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPAMD8	ENST00000443236.7	TSL:1 MANE Select	c.5521G>A	p.Ala1841Thr	missense	Exon 42 of 42	ENSP00000402505.3	Q8IZJ3-1
CPAMD8	ENST00000942844.1		c.5485G>A	p.Ala1829Thr	missense	Exon 42 of 42	ENSP00000612903.1
CPAMD8	ENST00000651564.2		c.*1171G>A		3_prime_UTR	Exon 42 of 42	ENSP00000498697.2	Q8IZJ3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1422704

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

704332

African (AFR)

AF:

0.00

AC:

AN:

32430

American (AMR)

AF:

0.00

AC:

AN:

39902

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25438

East Asian (EAS)

AF:

0.00

AC:

AN:

37680

South Asian (SAS)

AF:

0.00

AC:

AN:

81682

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49762

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1091314

Other (OTH)

AF:

0.00

AC:

AN:

58810

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

8.2

(source)

DANN

Benign

0.97

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.43

M_CAP

Benign

0.0053

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.94

PhyloP100

0.76

PrimateAI

Benign

0.33

PROVEAN

Benign

0.60

Sift

Benign

0.047

Sift4G

Pathogenic

0.0

Vest4

0.31

MVP

0.24

MPC

0.059

ClinPred

0.27

GERP RS

1.6

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over