9-128310956-T-A

Position:

• chr9-128310956-T-A

Variant summary

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

The NM_015679.3(TRUB2):​c.601A>T​(p.Met201Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TRUB2 NM_015679.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.54

Genes affected

TRUB2 (HGNC:17170): (TruB pseudouridine synthase family member 2) Pseudouridine is an abundant component of rRNAs and tRNAs and is enzymatically generated by isomerization of uridine by pseudouridine synthase (Zucchini et al., 2003 [PubMed 12736709]).[supplied by OMIM, Mar 2008]

TRUB2 (HGNC:):

SWI5 (HGNC:31412): (SWI5 homologous recombination repair protein) Involved in cellular response to ionizing radiation and double-strand break repair via homologous recombination. Part of Swi5-Sfr1 complex. [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=0.1425285).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRUB2	NM_015679.3	c.601A>T	p.Met201Leu	missense_variant	7/8	ENST00000372890.6	NP_056494.1
TRUB2	NM_001329861.2	c.469A>T	p.Met157Leu	missense_variant	6/7		NP_001316790.1
TRUB2	NM_001329862.2	c.433A>T	p.Met145Leu	missense_variant	7/8		NP_001316791.1
TRUB2	NM_001329863.2	c.289A>T	p.Met97Leu	missense_variant	8/9		NP_001316792.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRUB2	ENST00000372890.6	c.601A>T	p.Met201Leu	missense_variant	7/8	1	NM_015679.3	ENSP00000361982.4
TRUB2	ENST00000460320.1	n.681A>T		non_coding_transcript_exon_variant	8/9	2
TRUB2	ENST00000461180.1	n.399A>T		non_coding_transcript_exon_variant	1/2	2
SWI5	ENST00000652598.1	n.329-2874T>A		intron_variant				ENSP00000498805.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461892 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Apr 19, 2024

The c.601A>T (p.M201L) alteration is located in exon 7 (coding exon 7) of the TRUB2 gene. This alteration results from a A to T substitution at nucleotide position 601, causing the methionine (M) at amino acid position 201 to be replaced by a leucine (L). 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	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.0086	T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.039
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.096
Sift	Benign	0.16	T
Sift4G	Benign	0.30	T
Polyphen		0.059	B
Vest4		0.27
MutPred		0.54		Loss of MoRF binding (P = 0.0787);
MVP		0.072
MPC		0.18
ClinPred		0.49	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.43

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: chr9-131073235;