Variant chr1-196779898-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021023.6(CFHR3):c.355G>C(p.Gly119Arg) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G119A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 25)

Exomes 𝑓: 0.0000029 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

CFHR3
NM_021023.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.167

Variant links:

Genes affected

CFHR3 (HGNC:16980): (complement factor H related 3) The protein encoded by this gene is a secreted protein, which belongs to the complement factor H-related protein family. It binds to heparin, and may be involved in complement regulation. Mutations in this gene are associated with decreased risk of age-related macular degeneration, and with an increased risk of atypical hemolytic-uremic syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

CFHR3 links:

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ACMG classification

Classification made for transcript

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=0.16670558).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR3	NM_021023.6 linkuse as main transcript	c.355G>C	p.Gly119Arg	missense_variant	3/6	ENST00000367425.9
CFHR3	NM_001166624.2 linkuse as main transcript	c.355G>C	p.Gly119Arg	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR3	ENST00000367425.9 linkuse as main transcript	c.355G>C	p.Gly119Arg	missense_variant	3/6	1	NM_021023.6	P1	Q02985-1
CFHR3	ENST00000471440.6 linkuse as main transcript	c.355G>C	p.Gly119Arg	missense_variant	3/5	1
CFHR3	ENST00000391985.7 linkuse as main transcript	c.355G>C	p.Gly119Arg	missense_variant	3/5	2			Q02985-2
CFHR3	ENST00000367427.7 linkuse as main transcript	c.355G>C	p.Gly119Arg	missense_variant, NMD_transcript_variant	3/7	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000838

AC:

AN:

238674

Hom.:

AF XY:

0.0000155

AC XY:

AN XY:

128656

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000184

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000286

AC:

AN:

1396500

Hom.:

Cov.:

AF XY:

0.00000577

AC XY:

AN XY:

693268

show subpopulations

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:

0.00000374

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000173

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Kidney disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Feb 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.8

DANN

Benign

0.66

DEOGEN2

Benign

0.035

T;T;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0039

LIST_S2

Benign

0.40

T;.;T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.2

L;.;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.1

N;N;N;.

REVEL

Benign

0.082

Sift

Uncertain

0.020

D;T;D;.

Sift4G

Benign

0.10

T;T;T;T

Polyphen

0.18

B;D;.;.

Vest4

0.069

MutPred

0.37

Loss of ubiquitination at K122 (P = 0.0481);Loss of ubiquitination at K122 (P = 0.0481);Loss of ubiquitination at K122 (P = 0.0481);Loss of ubiquitination at K122 (P = 0.0481);

MVP

0.41

MPC

0.53

ClinPred

0.21

GERP RS

1.2

Varity_R

0.063

gMVP

0.59

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

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