2-28850233-A-G

Position:

• chr2-28850233-A-G

Variant summary

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

The NM_017910.4(TRMT61B):​c.1400T>C​(p.Val467Ala) 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: 33)
• Consequence: TRMT61B NM_017910.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.92

Genes affected

TRMT61B (HGNC:26070): (tRNA methyltransferase 61B) Enables mRNA (adenine-N1-)-methyltransferase activity; rRNA (adenine) methyltransferase activity; and tRNA (adenine-N1-)-methyltransferase activity. Involved in mRNA methylation; mitochondrial tRNA methylation; and protein homooligomerization. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

SPDYA (HGNC:30613): (speedy/RINGO cell cycle regulator family member A) Enables protein kinase activator activity and protein kinase binding activity. Involved in several processes, including G1/S transition of mitotic cell cycle; positive regulation of cell population proliferation; and positive regulation of protein kinase activity. Located in nucleoplasm. [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	Protein	UniProt
TRMT61B	NM_017910.4	c.1400T>C	p.Val467Ala	missense_variant	7/7	ENST00000306108.10	NP_060380.3
SPDYA	NM_182756.4	c.*292A>G		3_prime_UTR_variant	8/8	ENST00000334056.10	NP_877433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT61B	ENST00000306108.10	c.1400T>C	p.Val467Ala	missense_variant	7/7	1	NM_017910.4	ENSP00000302801	P1
SPDYA	ENST00000334056.10	c.*292A>G		3_prime_UTR_variant	8/8	1	NM_182756.4	ENSP00000335628	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Feb 06, 2023

The c.1400T>C (p.V467A) alteration is located in exon 7 (coding exon 7) of the TRMT61B gene. This alteration results from a T to C substitution at nucleotide position 1400, causing the valine (V) at amino acid position 467 to be replaced by an alanine (A). 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	Uncertain	0.53
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.20
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.034	D
Polyphen		0.94	P
Vest4		0.54
MutPred		0.59		Gain of helix (P = 0.0082);
MVP		0.52
MPC		0.39
ClinPred		0.99	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.55
gMVP		0.56

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: chr2-29073099;