Variant 16-69424696-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_030579.3(CYB5B):c.13A>T(p.Met5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000182 in 1,587,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

CYB5B
NM_030579.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.21

Variant links:

Genes affected

CYB5B (HGNC:24374): (cytochrome b5 type B) Enables heme binding activity. Contributes to nitrite reductase (NO-forming) activity. Involved in nitric oxide biosynthetic process. Located in membrane. Part of nitric-oxide synthase complex. [provided by Alliance of Genome Resources, Apr 2022]

CYB5B links:

CYB5B (HGNC:):

CYB5B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.821

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYB5B	NM_030579.3 linkuse as main transcript	c.13A>T	p.Met5Leu	missense_variant	1/5	ENST00000307892.13	NP_085056.2	O43169

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYB5B	ENST00000307892.13 linkuse as main transcript	c.13A>T	p.Met5Leu	missense_variant	1/5	1	NM_030579.3	ENSP00000308430.8		O43169

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000101

AC:

AN:

226754

Hom.:

AF XY:

0.000146

AC XY:

AN XY:

123440

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:

0.000212

Gnomad OTH exome

AF:

0.000188

GnomAD4 exome

AF:

0.000186

AC:

267

AN:

1435516

Hom.:

Cov.:

AF XY:

0.000207

AC XY:

148

AN XY:

713382

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000243

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:

0.000227

Gnomad4 OTH exome

AF:

0.000287

GnomAD4 genome

AF:

0.000145

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000124

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000238

AC:

ExAC

AF:

0.0000992

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 13, 2024

The c.13A>T (p.M5L) alteration is located in exon 1 (coding exon 1) of the CYB5B gene. This alteration results from a A to T substitution at nucleotide position 13, causing the methionine (M) at amino acid position 5 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Pathogenic

0.20

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.019

T;.;T;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

D;T;D;D

M_CAP

Pathogenic

0.68

MetaRNN

Pathogenic

0.82

D;D;D;D

MetaSVM

Uncertain

0.55

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.66

N;N;N;N

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Benign

0.076

T;T;D;D

Polyphen

0.96

D;.;P;.

Vest4

0.89

MutPred

0.99

Gain of stability (P = 0.3174);.;Gain of stability (P = 0.3174);Gain of stability (P = 0.3174);

MVP

0.83

MPC

0.17

ClinPred

0.91

GERP RS

5.9

Varity_R

0.97

gMVP

0.35

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