Genetic Variant CYB561:p.Gly88Arg (chr17-63436093-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001915.4(CYB561):c.262G>C(p.Gly88Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,614,214 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

CYB561
NM_001915.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.86

Variant links:

Genes affected

CYB561 (HGNC:2571): (cytochrome b561) Predicted to enable transmembrane monodehydroascorbate reductase activity. Predicted to be involved in ascorbate homeostasis. Predicted to be located in chromaffin granule membrane. Predicted to be active in lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

CYB561 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYB561	NM_001915.4 link	c.262G>C	p.Gly88Arg	missense_variant	Exon 3 of 6	ENST00000360793.8	NP_001906.3	P49447-1
CYB561	NM_001330421.2 link	c.283G>C	p.Gly95Arg	missense_variant	Exon 3 of 6		NP_001317350.1	P49447J3QRH5
CYB561	NM_001017916.2 link	c.262G>C	p.Gly88Arg	missense_variant	Exon 3 of 6		NP_001017916.1	P49447-1B3KTA1
CYB561	NM_001017917.2 link	c.262G>C	p.Gly88Arg	missense_variant	Exon 3 of 6		NP_001017917.1	P49447-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYB561	ENST00000360793.8 link	c.262G>C	p.Gly88Arg	missense_variant	Exon 3 of 6	1	NM_001915.4	ENSP00000354028.3		P49447-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152228

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:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

251270

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135842

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:

0.000462

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727238

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:

0.000412

Gnomad4 NFE exome

AF:

0.00000629

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000459

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74498

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:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000577

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Benign

0.89

DEOGEN2

Benign

0.23

T;T;.;T;.;T;.;T;T;.;T;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

.;.;D;D;D;.;D;D;D;D;.;D

M_CAP

Benign

0.052

MetaRNN

Uncertain

0.69

D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.56

MutationAssessor

Uncertain

2.7

M;M;.;M;.;M;M;.;.;.;M;.

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.2

D;D;.;D;.;.;D;.;D;.;.;.

REVEL

Uncertain

0.39

Sift

Uncertain

0.0030

D;D;.;D;.;.;D;.;D;.;.;.

Sift4G

Uncertain

0.030

D;D;D;D;T;D;D;D;D;D;.;.

Polyphen

1.0

D;D;.;D;.;D;.;.;D;.;D;.

Vest4

0.73

MutPred

0.74

.;.;.;.;.;.;.;.;Gain of MoRF binding (P = 0.0086);.;.;.;

MVP

0.33

MPC

1.1

ClinPred

0.87

GERP RS

4.9

Varity_R

0.55

gMVP

0.77

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over