chr1-109495812-C-G

Position:

• chr1-109495812-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182580.3(CYB561D1):​c.243C>G​(p.Phe81Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,612 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CYB561D1 NM_182580.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18364298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYB561D1	NM_182580.3	c.243C>G	p.Phe81Leu	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.243C>G	p.Phe81Leu	missense_variant	3/3	1	NM_182580.3	ENSP00000413530.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461612 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727116

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Nov 03, 2022

The c.309C>G (p.F103L) 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 309, causing the phenylalanine (F) at amino acid position 103 to be replaced by a leucine (L). 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	Pathogenic	0.58
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.011	.;T;T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.72	T;T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-0.29	T
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.74	N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.82	T;T;T;T
Sift4G	Benign	0.14	T;T;T;T
Polyphen		0.77, 1.0	.;P;.;D
Vest4		0.31
MutPred		0.49		.;Gain of helix (P = 0.132);Gain of helix (P = 0.132);.;
MVP		0.18
MPC		0.54
ClinPred		0.95	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.37

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

Other links and lift over

dbSNP: rs1657502440; hg19: chr1-110038434;