1-19254829-C-G

Variant names:

• chr1-19254829-C-G
• NM_016183.4:c.76C>G

Variant summary

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

The NM_016183.4(MRTO4):​c.76C>G​(p.Leu26Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRTO4 NM_016183.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.08

Genes affected

MRTO4 (HGNC:18477): (MRT4 homolog, ribosome maturation factor) This gene encodes a protein sharing a low level of sequence similarity with ribosomal protein P0. While the precise function of the encoded protein is currently unknown, it appears to be involved in mRNA turnover and ribosome assembly. [provided by RefSeq, Jul 2008]

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 rank	MANE	Protein	UniProt
MRTO4	NM_016183.4	c.76C>G	p.Leu26Val	missense_variant	Exon 2 of 8	ENST00000330263.5	NP_057267.2
MRTO4	XM_006710675.5	c.-66C>G		5_prime_UTR_variant	Exon 2 of 8		XP_006710738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRTO4	ENST00000330263.5	c.76C>G	p.Leu26Val	missense_variant	Exon 2 of 8	1	NM_016183.4	ENSP00000364320.3
MRTO4	ENST00000493700.1	n.462C>G		non_coding_transcript_exon_variant	Exon 2 of 3	2

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

Feb 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.76C>G (p.L26V) alteration is located in exon 2 (coding exon 2) of the MRTO4 gene. This alteration results from a C to G substitution at nucleotide position 76, causing the leucine (L) at amino acid position 26 to be replaced by a valine (V). 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	0.40
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.27
Sift	Benign	0.12	T
Sift4G	Uncertain	0.048	D
Polyphen		0.92	P
Vest4		0.58
MutPred		0.53		Gain of MoRF binding (P = 0.0777);
MVP		0.43
MPC		0.27
ClinPred		0.93	D
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.36

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: chr1-19581323;