1-19257905-T-A

Variant names:

• chr1-19257905-T-A
• NM_016183.4:c.414T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016183.4(MRTO4):​c.414T>A​(p.Asp138Glu) variant causes a missense 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. 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: 32)
• Consequence: MRTO4 NM_016183.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.372
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.100866735).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016183.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRTO4	NM_016183.4	MANE Select	c.414T>A	p.Asp138Glu	missense	Exon 6 of 8	NP_057267.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRTO4	ENST00000330263.5	TSL:1 MANE Select	c.414T>A	p.Asp138Glu	missense	Exon 6 of 8	ENSP00000364320.3	Q9UKD2
	MRTO4	ENST00000857508.1		c.414T>A	p.Asp138Glu	missense	Exon 6 of 8	ENSP00000527567.1
	MRTO4	ENST00000933910.1		c.387T>A	p.Asp129Glu	missense	Exon 6 of 8	ENSP00000603969.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	2.8
DANN	Benign	0.61
DEOGEN2	Benign	0.064	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.72	N
PhyloP100		-0.37
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.14
Sift	Benign	0.44	T
Sift4G	Benign	0.79	T
Polyphen		0.0040	B
Vest4		0.42
MutPred		0.35		Gain of disorder (P = 0.0915)
MVP		0.30
MPC		0.044
ClinPred		0.078	T
GERP RS		-5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.043
gMVP		0.43
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr1-19584399;