rs140262959

chr13-27440036-T-Cchr13-27440036-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_152912.5(MTIF3):c.413A>G(p.Gln138Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00979 in 1,614,238 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0072 (7 hom., cov: 32)
  • Exomes 𝑓: 0.010 (88 hom.)
• Consequence: MTIF3 NM_152912.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.84

Genes affected

MTIF3 (HGNC:29788): (mitochondrial translational initiation factor 3) This gene encodes a translation initiation factor that is involved in mitochondrial protein synthesis. Polymorphism in this gene is associated with the onset of Parkinson's disease. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 5. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007491678).
• BP6: Variant 13-27440036-T-C is Benign according to our data. Variant chr13-27440036-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 445609.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-27440036-T-C is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTIF3	NM_152912.5	c.413A>G	p.Gln138Arg	missense_variant	3/5	ENST00000381120.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTIF3	ENST00000381120.8	c.413A>G	p.Gln138Arg	missense_variant	3/5	1	NM_152912.5	P1

Frequencies

GnomAD3 genomes AF: 0.00725 AC: 1103 AN: 152228 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00239

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00556

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0110

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00772 AC: 1941 AN: 251482 Hom.: 13 AF XY: 0.00801 AC XY: 1089 AN XY: 135912

Gnomad AFR exome AF: 0.00172

Gnomad AMR exome AF: 0.00460

Gnomad ASJ exome AF: 0.00357

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000915

Gnomad FIN exome AF: 0.0114

Gnomad NFE exome AF: 0.0122

Gnomad OTH exome AF: 0.00929

GnomAD4 exome AF: 0.0101 AC: 14706 AN: 1461892 Hom.: 88 Cov.: 32 AF XY: 0.0100 AC XY: 7269 AN XY: 727246

Gnomad4 AFR exome AF: 0.00140

Gnomad4 AMR exome AF: 0.00478

Gnomad4 ASJ exome AF: 0.00409

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000974

Gnomad4 FIN exome AF: 0.0105

Gnomad4 NFE exome AF: 0.0119

Gnomad4 OTH exome AF: 0.00791

GnomAD4 genome AF: 0.00723 AC: 1102 AN: 152346 Hom.: 7 Cov.: 32 AF XY: 0.00701 AC XY: 522 AN XY: 74504

Gnomad4 AFR AF: 0.00238

Gnomad4 AMR AF: 0.00556

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0126

Gnomad4 NFE AF: 0.0110

Gnomad4 OTH AF: 0.00992

Alfa AF: 0.0101 Hom.: 12

Bravo AF: 0.00695

TwinsUK AF: 0.00944 AC: 35

ALSPAC AF: 0.00830 AC: 32

ESP6500AA AF: 0.00272 AC: 12

ESP6500EA AF: 0.0117 AC: 101

ExAC AF: 0.00814 AC: 988

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0109

EpiControl AF: 0.0117

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Aug 15, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	20
Dann	Uncertain	0.98
DEOGEN2	Benign	0.038	T;T;T
Eigen	Benign	0.069
Eigen_PC	Benign	0.067
FATHMM_MKL	Pathogenic	0.99	D
MetaRNN	Benign	0.0075	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.3	M;M;M
MutationTaster	Benign	0.61	D;D;D;D
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.0090	D;D;D
Sift4G	Uncertain	0.011	D;D;D
Polyphen		0.67	P;P;P
Vest4		0.14
MVP		0.46
MPC		0.36
ClinPred		0.017	T
GERP RS		6.0
Varity_R		0.14
gMVP		0.38

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

LitVar

Other links and lift over

dbSNP: rs140262959; hg19: chr13-28014173;