1-19258541-G-T

Variant names:

• chr1-19258541-G-T
• NM_016183.4:c.558G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016183.4(MRTO4):​c.558G>T​(p.Gln186His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q186P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRTO4 NM_016183.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.61

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.859

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRTO4	NM_016183.4	c.558G>T	p.Gln186His	missense_variant	Exon 7 of 8	ENST00000330263.5	NP_057267.2
MRTO4	XM_006710675.5	c.417G>T	p.Gln139His	missense_variant	Exon 7 of 8		XP_006710738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRTO4	ENST00000330263.5	c.558G>T	p.Gln186His	missense_variant	Exon 7 of 8	1	NM_016183.4	ENSP00000364320.3
MRTO4	ENST00000479559.1	n.338G>T		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

Nov 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.558G>T (p.Q186H) alteration is located in exon 7 (coding exon 7) of the MRTO4 gene. This alteration results from a G to T substitution at nucleotide position 558, causing the glutamine (Q) at amino acid position 186 to be replaced by a histidine (H). 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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	0.019	D
MutationAssessor	Pathogenic	3.3	M
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.65		Gain of helix (P = 0.0854);
MVP		0.75
MPC		0.30
ClinPred		0.99	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.69
gMVP		0.73

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: chr1-19585035;