Variant 1-54190817-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001031672.4(CYB5RL):c.278A>C(p.Tyr93Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000347 in 1,441,580 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

CYB5RL
NM_001031672.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

Variant links:

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]

CYB5RL links:

ENSG00000256407 (HGNC:):

ENSG00000256407 links:

MRPL37 (HGNC:14034): (mitochondrial ribosomal protein L37) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. [provided by RefSeq, Jul 2008]

MRPL37 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/exons	MANE	Protein	UniProt
CYB5RL	NM_001031672.4 link	c.278A>C	p.Tyr93Ser	missense_variant	4/8	ENST00000534324.6	NP_001026842.2	Q6IPT4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYB5RL	ENST00000534324.6 link	c.278A>C	p.Tyr93Ser	missense_variant	4/8	5	NM_001031672.4	ENSP00000434343.1		Q6IPT4-1
ENSG00000256407	ENST00000637610.1 link	n.198+4602A>C		intron_variant		5		ENSP00000490901.1		A0A1B0GWF0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000461

AC:

AN:

216846

Hom.:

AF XY:

0.00

AC XY:

AN XY:

116702

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:

0.0000377

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000347

AC:

AN:

1441580

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

714962

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:

0.0000242

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000272

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

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

Aug 11, 2024

The c.278A>C (p.Y93S) alteration is located in exon 4 (coding exon 2) of the CYB5RL gene. This alteration results from a A to C substitution at nucleotide position 278, causing the tyrosine (Y) at amino acid position 93 to be replaced by a serine (S). 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

0.15

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.060

.;T;.;.

Eigen

Benign

-0.070

Eigen_PC

Benign

-0.045

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.82

T;T;T;T

M_CAP

Benign

0.047

MetaRNN

Uncertain

0.45

T;T;T;T

MetaSVM

Benign

-0.43

MutationAssessor

Benign

1.5

L;L;.;.

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.3

N;N;N;N

REVEL

Uncertain

0.57

Sift

Benign

0.37

T;T;T;D

Sift4G

Benign

0.23

T;T;T;T

Polyphen

0.78

.;P;.;.

Vest4

0.83

MutPred

0.56

Gain of disorder (P = 0.0339);Gain of disorder (P = 0.0339);.;Gain of disorder (P = 0.0339);

MVP

0.53

ClinPred

0.31

GERP RS

3.9

Varity_R

0.17

gMVP

0.68

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