chr1-54179172-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001031672.4(CYB5RL):c.721C>G(p.Arg241Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,818 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: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
CYB5RL
NM_001031672.4 missense
NM_001031672.4 missense
Scores
3
9
7
Clinical Significance
Conservation
PhyloP100: 2.05
Genes affected
CYB5RL (HGNC:32220): (cytochrome b5 reductase like) Predicted to enable cytochrome-b5 reductase activity, acting on NAD(P)H. Predicted to be involved in bicarbonate transport. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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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, 0.767
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYB5RL | NM_001031672.4 | c.721C>G | p.Arg241Gly | missense_variant | 7/8 | ENST00000534324.6 | |
CYB5RL | NM_001353353.2 | c.484C>G | p.Arg162Gly | missense_variant | 5/6 | ||
CYB5RL | NM_001353354.2 | c.277C>G | p.Arg93Gly | missense_variant | 6/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYB5RL | ENST00000534324.6 | c.721C>G | p.Arg241Gly | missense_variant | 7/8 | 5 | NM_001031672.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000162 AC: 4AN: 247656Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134314
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460818Hom.: 0 Cov.: 31 AF XY: 0.00000964 AC XY: 7AN XY: 726516
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ExAC
?
AF:
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1
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 | Oct 10, 2023 | The c.721C>G (p.R241G) alteration is located in exon 7 (coding exon 5) of the CYB5RL gene. This alteration results from a C to G substitution at nucleotide position 721, causing the arginine (R) at amino acid position 241 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
MutPred
Loss of sheet (P = 0.0817);.;
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at