NM_001031672.4:c.266C>G

Variant names:

• chr1-54190829-G-C
• rs1413186021
• NM_001031672.4:c.266C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001031672.4(CYB5RL):​c.266C>G​(p.Thr89Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000758 in 1,450,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 0.0000076 (0 hom.)
• Consequence: CYB5RL NM_001031672.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.00
• Publications: 0 publications found

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]

ENSG00000256407 (HGNC:):

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18781301).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031672.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5RL	NM_001031672.4	MANE Select	c.266C>G	p.Thr89Ser	missense	Exon 4 of 8	NP_001026842.2	Q6IPT4-1
	CYB5RL	NM_001353356.2		c.266C>G	p.Thr89Ser	missense	Exon 4 of 4	NP_001340285.1	E9PMD3
	CYB5RL	NM_001353353.2		c.198+4590C>G		intron	N/A	NP_001340282.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5RL	ENST00000534324.6	TSL:5 MANE Select	c.266C>G	p.Thr89Ser	missense	Exon 4 of 8	ENSP00000434343.1	Q6IPT4-1
	CYB5RL	ENST00000528287.5	TSL:1	n.266C>G		non_coding_transcript_exon	Exon 4 of 8	ENSP00000431428.1	E9PL89
	CYB5RL	ENST00000420054.5	TSL:1	n.154-3090C>G		intron	N/A	ENSP00000403021.1	F8WDU4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000758 AC: 11 AN: 1450522 Hom.: 0 Cov.: 30 AF XY: 0.00000694 AC XY: 5 AN XY: 720338

African (AFR) AF: 0.00 AC: 0 AN: 33320

American (AMR) AF: 0.00 AC: 0 AN: 42888

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25856

East Asian (EAS) AF: 0.00 AC: 0 AN: 39234

South Asian (SAS) AF: 0.00 AC: 0 AN: 83864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000994 AC: 11 AN: 1106986

Other (OTH) AF: 0.00 AC: 0 AN: 59994

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Benign	0.64
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.20	N
PhyloP100		6.0
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.29
Sift	Benign	0.74	T
Sift4G	Benign	0.36	T
Polyphen		0.23	B
Vest4		0.33
MutPred		0.42		Gain of phosphorylation at Y93 (P = 0.132)
MVP		0.35
ClinPred		0.47	T
GERP RS		5.0
Varity_R		0.11
gMVP		0.49
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1413186021; hg19: chr1-54656502;