rs370553422

Variant names:

• chr10-133394236-C-A
• rs370553422
• NM_138384.4:c.16C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-133394236-C-A
• chr10-133394236-C-G
• chr10-133394236-C-T

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.16C>A​(p.Arg6Ser) 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 1,364,356 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. R6C) 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: 1.86
• 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=0.124673724).

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.16C>A	p.Arg6Ser	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.16C>A	p.Arg6Ser	missense	Exon 1 of 11	ENSP00000323047.6	Q9BT17-1
	MTG1	ENST00000477902.6	TSL:3	c.-12+52C>A		intron	N/A	ENSP00000475596.1	U3KQ69
	ENSG00000254536	ENST00000468317.3	TSL:5	n.*37-1477C>A		intron	N/A	ENSP00000436767.2	B0QZA9

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.33e-7 AC: 1 AN: 1364356 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 673216

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27938

American (AMR) AF: 0.00 AC: 0 AN: 33878

Ashkenazi Jewish (ASJ) AF: 0.0000413 AC: 1 AN: 24226

East Asian (EAS) AF: 0.00 AC: 0 AN: 32042

South Asian (SAS) AF: 0.00 AC: 0 AN: 77306

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38982

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4138

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069042

Other (OTH) AF: 0.00 AC: 0 AN: 56804

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.9
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.055
Sift	Benign	0.039	D
Sift4G	Benign	0.090	T
Polyphen		0.042	B
Vest4		0.36
MutPred		0.37		Loss of MoRF binding (P = 2e-04)
MVP		0.25
MPC		0.026
ClinPred		0.26	T
GERP RS		0.75
PromoterAI		0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.10
gMVP		0.39
Mutation Taster		=91/9	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: rs370553422; hg19: chr10-135207740;