NM_016183.4:c.23A>G

Variant names:

• chr1-19251858-A-G
• rs1380357457
• NM_016183.4:c.23A>G

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.23A>G​(p.Lys8Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,439,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K8T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MRTO4 NM_016183.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.52
• 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=0.19584638).

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.23A>G	p.Lys8Arg	missense	Exon 1 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.23A>G	p.Lys8Arg	missense	Exon 1 of 8	ENSP00000364320.3	Q9UKD2
	MRTO4	ENST00000857508.1		c.23A>G	p.Lys8Arg	missense	Exon 1 of 8	ENSP00000527567.1
	MRTO4	ENST00000933910.1		c.23A>G	p.Lys8Arg	missense	Exon 1 of 8	ENSP00000603969.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1439562 Hom.: 0 Cov.: 31 AF XY: 0.00000280 AC XY: 2 AN XY: 714138

African (AFR) AF: 0.00 AC: 0 AN: 33016

American (AMR) AF: 0.00 AC: 0 AN: 41658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25706

East Asian (EAS) AF: 0.00 AC: 0 AN: 38496

South Asian (SAS) AF: 0.00 AC: 0 AN: 83064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1101784

Other (OTH) AF: 0.00 AC: 0 AN: 59490

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.3	L
PhyloP100		3.5
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.090
Sift	Benign	0.12	T
Sift4G	Benign	0.11	T
Polyphen		0.72	P
Vest4		0.056
MutPred		0.41		Loss of methylation at K8 (P = 0.005)
MVP		0.58
MPC		0.047
ClinPred		0.79	D
GERP RS		5.1
PromoterAI		-0.018	Neutral
Varity_R		0.11
gMVP		0.32
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs1380357457; hg19: chr1-19578352;