2-199933071-T-A

Position:

• chr2-199933071-T-A

Variant summary

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

The NM_001039693.3(TYW5):​c.944A>T​(p.Glu315Val) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TYW5 NM_001039693.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.10

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]

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=0.19700348).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYW5	NM_001039693.3	c.944A>T	p.Glu315Val	missense_variant	8/8	ENST00000354611.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYW5	ENST00000354611.9	c.944A>T	p.Glu315Val	missense_variant	8/8	1	NM_001039693.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0093	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	0.94	D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.049
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.013	D
Polyphen		0.79	P
Vest4		0.25
MutPred		0.33		Gain of MoRF binding (P = 0.0307);
MVP		0.20
MPC		0.32
ClinPred		0.71	D
GERP RS		5.8
Varity_R		0.18
gMVP		0.61

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: chr2-200797794;