chr1-109496140-C-G

Position:

• chr1-109496140-C-G

Variant summary

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

The NM_182580.3(CYB561D1):​c.571C>G​(p.Gln191Glu) variant causes a missense change involving the alteration of a non-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: CYB561D1 NM_182580.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.21

Genes affected

CYB561D1 (HGNC:26804): (cytochrome b561 family member D1) Predicted to enable heme binding activity and oxidoreductase activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.32291776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYB561D1	NM_182580.3	c.571C>G	p.Gln191Glu	missense_variant	3/3	ENST00000420578.7	NP_872386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYB561D1	ENST00000420578.7	c.571C>G	p.Gln191Glu	missense_variant	3/3	1	NM_182580.3	ENSP00000413530.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Jan 03, 2024

The c.637C>G (p.Q213E) alteration is located in exon 3 (coding exon 3) of the CYB561D1 gene. This alteration results from a C to G substitution at nucleotide position 637, causing the glutamine (Q) at amino acid position 213 to be replaced by a glutamic acid (E). 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	0.14
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	.;T;T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.90	D;T;T;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.6	.;M;.;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.93	N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.089	T;T;T;T
Sift4G	Benign	0.24	T;T;T;T
Polyphen		1.0, 1.0	.;D;.;D
Vest4		0.51
MutPred		0.47		.;Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);.;
MVP		0.19
MPC		0.98
ClinPred		0.79	D
GERP RS		5.3
Varity_R		0.31
gMVP		0.62

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: chr1-110038762;