Genetic Variant NM_144611.4:c.388G>T (chr17-4150028-G-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_144611.4(CYB5D2):c.388G>T(p.Val130Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,676 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: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

CYB5D2
NM_144611.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33

Publications

0 publications found

Variant links:

Genes affected

CYB5D2 (HGNC:28471): (cytochrome b5 domain containing 2) Predicted to enable heme binding activity. Predicted to be involved in nervous system development. Predicted to act upstream of or within positive regulation of neuron differentiation. Predicted to be located in extracellular region. Predicted to be active in endomembrane system and membrane. [provided by Alliance of Genome Resources, Apr 2022]

CYB5D2 links:

ENSG00000308322 (HGNC:):

ENSG00000308322 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.925

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144611.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYB5D2	NM_144611.4	MANE Select	c.388G>T	p.Val130Phe	missense	Exon 2 of 4	NP_653212.1	Q8WUJ1-1
CYB5D2	NM_001254755.2		c.52G>T	p.Val18Phe	missense	Exon 2 of 4	NP_001241684.1	Q8WUJ1-3
CYB5D2	NM_001254756.1		c.52G>T	p.Val18Phe	missense	Exon 2 of 4	NP_001241685.1	Q8WUJ1-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYB5D2	ENST00000301391.8	TSL:1 MANE Select	c.388G>T	p.Val130Phe	missense	Exon 2 of 4	ENSP00000301391.4	Q8WUJ1-1
CYB5D2	ENST00000575251.5	TSL:2	c.52G>T	p.Val18Phe	missense	Exon 2 of 4	ENSP00000458903.1	Q8WUJ1-3
CYB5D2	ENST00000577075.6	TSL:2	c.52G>T	p.Val18Phe	missense	Exon 2 of 4	ENSP00000458352.2	Q8WUJ1-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251438

AF XY:

0.0000221

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461676

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727156

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.000139

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.000177

AC:

AN:

5642

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111998

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Uncertain

0.098

BayesDel_noAF

Pathogenic

0.14

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.92

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.76

M_CAP

Pathogenic

0.40

MetaRNN

Pathogenic

0.92

MetaSVM

Uncertain

0.64

MutationAssessor

Pathogenic

3.6

PhyloP100

3.3

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.9

REVEL

Pathogenic

0.73

Sift

Uncertain

0.010

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.71

MutPred

0.74

Gain of ubiquitination at K125 (P = 0.135)

MVP

0.42

MPC

0.70

ClinPred

0.94

GERP RS

3.4

Varity_R

0.52

gMVP

0.91

Mutation Taster

=53/47

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over