3-149179606-C-T

Position:

chr3-149179606-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_000096.4(CP):c.2611G>A(p.Asp871Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000407 in 1,613,696 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00043 ( 13 hom. )

Consequence

CP
NM_000096.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 4.33

Variant links:

Genes affected

CP (HGNC:2295): (ceruloplasmin) The protein encoded by this gene is a metalloprotein that binds most of the copper in plasma and is involved in the peroxidation of Fe(II)transferrin to Fe(III) transferrin. Mutations in this gene cause aceruloplasminemia, which results in iron accumulation and tissue damage, and is associated with diabetes and neurologic abnormalities. Two transcript variants, one protein-coding and the other not protein-coding, have been found for this gene. [provided by RefSeq, Feb 2012]

CP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009948522).

BP6

Variant 3-149179606-C-T is Benign according to our data. Variant chr3-149179606-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 343753.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CP	NM_000096.4 linkuse as main transcript	c.2611G>A	p.Asp871Asn	missense_variant	15/19	ENST00000264613.11	NP_000087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CP	ENST00000264613.11 linkuse as main transcript	c.2611G>A	p.Asp871Asn	missense_variant	15/19	1	NM_000096.4	ENSP00000264613	P1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000963

AC:

242

AN:

251260

Hom.:

AF XY:

0.00122

AC XY:

166

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00715

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000432

AC:

632

AN:

1461592

Hom.:

Cov.:

AF XY:

0.000597

AC XY:

434

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00589

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000863

Gnomad4 OTH exome

AF:

0.000397

GnomAD4 genome

AF:

0.000164

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00478

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000125

Hom.:

Bravo

AF:

0.0000416

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00107

AC:

130

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Deficiency of ferroxidase

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 11, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Feb 22, 2017

- -

CP-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 02, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.22

T;.;D

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.90

D;.;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.0099

T;T;T

MetaSVM

Pathogenic

0.97

MutationTaster

Benign

1.0

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-4.2

D;D;D

REVEL

Uncertain

0.52

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Vest4

0.54

MutPred

0.49

.;Loss of catalytic residue at D871 (P = 0.0201);.;

MVP

0.97

MPC

0.43

ClinPred

0.26

GERP RS

5.7

gMVP

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over