CYB5A p.Val123Val

Variant names:

• chr18-74253619-C-C
• NM_148923.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr18-74253620--
• chr18-74253620-G-A
• chr18-74253620-G-T
• chr18-74253620-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_148923.4(CYB5A):​c. variant causes a exon region 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: 33)
• Consequence: CYB5A NM_148923.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 0 publications found

Genes affected

CYB5A (HGNC:2570): (cytochrome b5 type A) The protein encoded by this gene is a membrane-bound cytochrome that reduces ferric hemoglobin (methemoglobin) to ferrous hemoglobin, which is required for stearyl-CoA-desaturase activity. Defects in this gene are a cause of type IV hereditary methemoglobinemia. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

CYB5A Gene-Disease associations (from GenCC):

• methemoglobinemia type 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• 46,XY disorder of sex development due to isolated 17,20-lyase deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_148923.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5A	NM_148923.4	MANE Select	c.		exon_region	Exon 5 of 5	NP_683725.1	P00167-1
	CYB5A	NM_001190807.3		c.		exon_region	Exon 4 of 4	NP_001177736.1	P00167-3
	CYB5A	NM_001914.4		c.		exon_region	Exon 6 of 6	NP_001905.1	P00167-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5A	ENST00000340533.9	TSL:1 MANE Select	c.		exon_region	Exon 5 of 5	ENSP00000341625.4	P00167-1
	CYB5A	ENST00000494131.6	TSL:1	c.		exon_region	Exon 6 of 6	ENSP00000436461.2	P00167-2
	CYB5A	ENST00000494131.6	TSL:1	c.		3_prime_UTR	Exon 6 of 6	ENSP00000436461.2	P00167-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr18-71920854;