chr2-199948429-G-T

Position:

• chr2-199948429-G-T

Variant summary

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

The NM_001039693.3(TYW5):​c.122C>A​(p.Thr41Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TYW5 NM_001039693.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.57

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYW5	NM_001039693.3	c.122C>A	p.Thr41Lys	missense_variant	2/8	ENST00000354611.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYW5	ENST00000354611.9	c.122C>A	p.Thr41Lys	missense_variant	2/8	1	NM_001039693.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Sep 29, 2023

The c.122C>A (p.T41K) alteration is located in exon 2 (coding exon 2) of the TYW5 gene. This alteration results from a C to A substitution at nucleotide position 122, causing the threonine (T) at amino acid position 41 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	0.10
BayesDel_addAF	Benign	0.0096	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	0.73	D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.37
Sift	Benign	0.12	T
Sift4G	Benign	0.12	T
Polyphen		0.77	P
Vest4		0.59
MutPred		0.66		Gain of methylation at T41 (P = 0.0101);
MVP		0.48
MPC		0.074
ClinPred		0.65	D
GERP RS		4.9
Varity_R		0.23
gMVP		0.69

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: chr2-200813152;