21-36135361-C-T

Position:

• chr21-36135361-C-T

Variant summary

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

The NM_001236.4(CBR3):​c.169C>T​(p.Pro57Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: CBR3 NM_001236.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.06

Genes affected

CBR3 (HGNC:1549): (carbonyl reductase 3) Carbonyl reductase 3 catalyzes the reduction of a large number of biologically and pharmacologically active carbonyl compounds to their corresponding alcohols. The enzyme is classified as a monomeric NADPH-dependent oxidoreductase. CBR3 contains three exons spanning 11.2 kilobases and is closely linked to another carbonyl reductase gene - CBR1. [provided by RefSeq, Jul 2008]

CBR3-AS1 (HGNC:):

ACMG classification

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
CBR3	NM_001236.4	c.169C>T	p.Pro57Ser	missense_variant	1/3	ENST00000290354.6	NP_001227.1
CBR3	XM_011529772.3	c.169C>T	p.Pro57Ser	missense_variant	1/3		XP_011528074.1
CBR3-AS1	NR_038892.1	n.193-1600G>A		intron_variant
CBR3-AS1	NR_038893.1	n.193-2287G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBR3	ENST00000290354.6	c.169C>T	p.Pro57Ser	missense_variant	1/3	1	NM_001236.4	ENSP00000290354.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 09, 2024

The c.169C>T (p.P57S) alteration is located in exon 1 (coding exon 1) of the CBR3 gene. This alteration results from a C to T substitution at nucleotide position 169, causing the proline (P) at amino acid position 57 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	Uncertain	0.38
BayesDel_addAF	Benign	0.0092	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	0.27	D
MutationAssessor	Benign	1.2	L
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.022	D
Sift4G	Benign	0.21	T
Polyphen		0.99	D
Vest4		0.25
MutPred		0.63		Loss of sheet (P = 0.0817);
MVP		0.89
MPC		0.64
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.84
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-37507659;