2-199933124-AT-GC

Variant names:

• chr2-199933124-AT-GC
• NM_001039693.3:c.890_891delATinsGC
• TYW5 p.Tyr297Cys

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001039693.3(TYW5):​c.890_891delATinsGC​(p.Tyr297Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TYW5 NM_001039693.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.74
• Publications: 0 publications found

Genes affected

TYW5 (HGNC:26754): (tRNA-yW synthesizing protein 5) Enables several functions, including iron ion binding activity; protein homodimerization activity; and tRNAPhe (7-(3-amino-3-carboxypropyl)wyosine37-C2)-hydroxylase activity. Involved in wybutosine biosynthetic process. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

C2orf69 (HGNC:26799): (chromosome 2 open reading frame 69) Involved in oxidative phosphorylation. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

C2orf69 Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation deficiency 53

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039693.3. 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
	TYW5	NM_001039693.3	MANE Select	c.890_891delATinsGC	p.Tyr297Cys	missense	N/A	NP_001034782.1	A2RUC4-1
	TYW5	NR_004862.2		n.892_893delATinsGC		non_coding_transcript_exon	Exon 8 of 8
	TYW5	NR_109905.2		n.640_641delATinsGC		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYW5	ENST00000354611.9	TSL:1 MANE Select	c.890_891delATinsGC	p.Tyr297Cys	missense	N/A	ENSP00000346627.4	A2RUC4-1
	TYW5	ENST00000441832.1	TSL:1	n.*417_*418delATinsGC		non_coding_transcript_exon	Exon 7 of 7	ENSP00000398447.1	A8KAJ9
	TYW5	ENST00000483328.5	TSL:1	n.*505_*506delATinsGC		non_coding_transcript_exon	Exon 8 of 8	ENSP00000420024.1	A8KAJ9

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7

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: chr2-200797847;