10-133394234-C-A

Variant names:

• chr10-133394234-C-A
• rs1283218633
• NM_138384.4:c.14C>A

Variant summary

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

The NM_138384.4(MTG1):​c.14C>A​(p.Pro5Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000733 in 1,364,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. P5L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: MTG1 NM_138384.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 0 publications found

Genes affected

MTG1 (HGNC:32159): (mitochondrial ribosome associated GTPase 1) Enables GTPase activity. Involved in regulation of mitochondrial translation and regulation of respiratory system process. Located in mitochondrial inner membrane and mitochondrial ribosome. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000254536 (HGNC:):

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=0.14346093).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138384.4. 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
	MTG1	NM_138384.4	MANE Select	c.14C>A	p.Pro5Gln	missense	Exon 1 of 11	NP_612393.2	Q9BT17-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTG1	ENST00000317502.11	TSL:1 MANE Select	c.14C>A	p.Pro5Gln	missense	Exon 1 of 11	ENSP00000323047.6	Q9BT17-1
	MTG1	ENST00000477902.6	TSL:3	c.-12+50C>A		intron	N/A	ENSP00000475596.1	U3KQ69
	ENSG00000254536	ENST00000468317.3	TSL:5	n.*37-1479C>A		intron	N/A	ENSP00000436767.2	B0QZA9

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.33e-7 AC: 1 AN: 1364332 Hom.: 0 Cov.: 31 AF XY: 0.00000149 AC XY: 1 AN XY: 673222

African (AFR) AF: 0.00 AC: 0 AN: 27956

American (AMR) AF: 0.00 AC: 0 AN: 33816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24248

East Asian (EAS) AF: 0.00 AC: 0 AN: 32078

South Asian (SAS) AF: 0.00 AC: 0 AN: 77332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 9.35e-7 AC: 1 AN: 1069040

Other (OTH) AF: 0.00 AC: 0 AN: 56776

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.6
DANN	Benign	0.93
DEOGEN2	Benign	0.033	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.058
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.088
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.028	D
Polyphen		0.45	B
Vest4		0.39
MutPred		0.26		Loss of methylation at R2 (P = 0.0355)
MVP		0.30
MPC		0.028
ClinPred		0.42	T
GERP RS		1.1
PromoterAI		0.060	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.089
gMVP		0.43
Mutation Taster		=96/4	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: rs1283218633; hg19: chr10-135207738;