4-8441121-T-C

Position:

• chr4-8441121-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001350233.2(TRMT44):​c.-396T>C variant causes a 5 prime UTR premature start codon gain 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRMT44 NM_001350233.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.50

Genes affected

TRMT44 (HGNC:26653): (tRNA methyltransferase 44 homolog) The protein encoded by this gene is a putative tRNA methyltransferase found in the cytoplasm. Defects in this gene may be a cause of partial epilepsy with pericentral spikes (PEPS), but that has not been proven definitively. [provided by RefSeq, May 2012]

TRMT44 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040661246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT44	NM_152544.3	c.299T>C	p.Leu100Pro	missense_variant	1/11	ENST00000389737.5	NP_689757.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT44	ENST00000389737.5	c.299T>C	p.Leu100Pro	missense_variant	1/11	5	NM_152544.3	ENSP00000374387.4
TRMT44	ENST00000513449.6	c.-76+2079T>C		intron_variant		1		ENSP00000424643.2
TRMT44	ENST00000504134.1	c.158T>C	p.Leu53Pro	missense_variant	1/2	3		ENSP00000434207.1
TRMT44	ENST00000528167.1	n.317T>C		non_coding_transcript_exon_variant	1/3	5

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

May 18, 2023

The c.299T>C (p.L100P) alteration is located in exon 1 (coding exon 1) of the TRMT44 gene. This alteration results from a T to C substitution at nucleotide position 299, causing the leucine (L) at amino acid position 100 to be replaced by a proline (P). 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	0.046
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.0
DANN	Benign	0.21
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.00043	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.00050	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.18	N
REVEL	Benign	0.010
Sift	Benign	0.23	T
Sift4G	Benign	0.089	T
Vest4		0.13
MutPred		0.27		Loss of helix (P = 3e-04);
MVP		0.030
MPC		0.028
ClinPred		0.085	T
GERP RS		-6.6
Varity_R		0.053
gMVP		0.053

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: chr4-8442848;