NM_144611.4:c.486C>A

Variant names:

• chr17-4154768-C-A
• NM_144611.4:c.486C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144611.4(CYB5D2):​c.486C>A​(p.Asn162Lys) 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. 16/21 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)
• Consequence: CYB5D2 NM_144611.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.00

Genes affected

CYB5D2 (HGNC:28471): (cytochrome b5 domain containing 2) Predicted to enable heme binding activity. Predicted to be involved in nervous system development. Predicted to act upstream of or within positive regulation of neuron differentiation. Predicted to be located in extracellular region. Predicted to be active in endomembrane system and membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC124903898 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043926448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYB5D2	NM_144611.4	c.486C>A	p.Asn162Lys	missense_variant	Exon 3 of 4	ENST00000301391.8	NP_653212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYB5D2	ENST00000301391.8	c.486C>A	p.Asn162Lys	missense_variant	Exon 3 of 4	1	NM_144611.4	ENSP00000301391.4

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

Feb 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.486C>A (p.N162K) alteration is located in exon 3 (coding exon 3) of the CYB5D2 gene. This alteration results from a C to A substitution at nucleotide position 486, causing the asparagine (N) at amino acid position 162 to be replaced by a lysine (K). 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	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.017
DANN	Benign	0.27
DEOGEN2	Benign	0.10	.;.;T;T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.37	.;T;T;T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.044	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.040	.;.;N;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	2.4	.;.;N;.
REVEL	Benign	0.13
Sift	Benign	1.0	.;.;T;.
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	.;.;B;.
Vest4		0.13
MutPred		0.32		.;.;Loss of stability (P = 0.0166);.;
MVP		0.014
MPC		0.16
ClinPred		0.018	T
GERP RS		-11
Varity_R		0.027
gMVP		0.39

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: chr17-4058062;