NM_024843.4:c.535A>G

Variant names:

• chr2-171553478-A-G
• NM_024843.4:c.535A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024843.4(CYBRD1):​c.535A>G​(p.Thr179Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CYBRD1 NM_024843.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.90

Genes affected

CYBRD1 (HGNC:20797): (cytochrome b reductase 1) This gene is a member of the cytochrome b(561) family that encodes an iron-regulated protein. It highly expressed in the duodenal brush border membrane. It has ferric reductase activity and is believed to play a physiological role in dietary iron absorption. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37943512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYBRD1	NM_024843.4	c.535A>G	p.Thr179Ala	missense_variant	Exon 3 of 4	ENST00000321348.9	NP_079119.3
CYBRD1	NM_001256909.2	c.361A>G	p.Thr121Ala	missense_variant	Exon 3 of 4		NP_001243838.1
CYBRD1	NM_001127383.2	c.326A>G	p.Asp109Gly	missense_variant	Exon 2 of 3		NP_001120855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYBRD1	ENST00000321348.9	c.535A>G	p.Thr179Ala	missense_variant	Exon 3 of 4	1	NM_024843.4	ENSP00000319141.4
CYBRD1	ENST00000375252.3	c.326A>G	p.Asp109Gly	missense_variant	Exon 2 of 3	1		ENSP00000364401.3
CYBRD1	ENST00000409484.5	c.361A>G	p.Thr121Ala	missense_variant	Exon 3 of 4	2		ENSP00000386739.1
CYBRD1	ENST00000445146.1	c.418A>G	p.Thr140Ala	missense_variant	Exon 3 of 4	3		ENSP00000402242.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.535A>G (p.T179A) alteration is located in exon 3 (coding exon 3) of the CYBRD1 gene. This alteration results from a A to G substitution at nucleotide position 535, causing the threonine (T) at amino acid position 179 to be replaced by an alanine (A). 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	0.39
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Pathogenic	0.35
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.38	T
MetaSVM	Uncertain	0.54	D
PROVEAN	Benign	0.17	N
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.37
MutPred		0.13		Gain of catalytic residue at I108 (P = 0.1244);
MVP		0.62
ClinPred		0.99	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: chr2-172409988;