Variant chr13-27435714-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_152912.5(MTIF3):c.798C>T(p.Asp266=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,613,172 control chromosomes in the GnomAD database, including 24,505 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 1911 hom., cov: 33)

Exomes 𝑓: 0.17 ( 22594 hom. )

Consequence

MTIF3
NM_152912.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.336

Variant links:

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]

MTIF3 links:

GTF3A (HGNC:4662): (general transcription factor IIIA) The product of this gene is a zinc finger protein with nine Cis[2]-His[2] zinc finger domains. It functions as an RNA polymerase III transcription factor to induce transcription of the 5S rRNA genes. The protein binds to a 50 bp internal promoter in the 5S genes called the internal control region (ICR), and nucleates formation of a stable preinitiation complex. This complex recruits the TFIIIC and TFIIIB transcription factors and RNA polymerase III to form the complete transcription complex. The protein is thought to be translated using a non-AUG translation initiation site in mammals based on sequence analysis, protein homology, and the size of the purified protein. [provided by RefSeq, Jul 2008]

GTF3A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP7

Synonymous conserved (PhyloP=-0.336 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTIF3	NM_152912.5 linkuse as main transcript	c.798C>T	p.Asp266=	synonymous_variant	5/5	ENST00000381120.8	NP_690876.3
GTF3A	NM_002097.3 linkuse as main transcript	c.*117G>A		3_prime_UTR_variant	9/9	ENST00000381140.10	NP_002088.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTIF3	ENST00000381120.8 linkuse as main transcript	c.798C>T	p.Asp266=	synonymous_variant	5/5	1	NM_152912.5	ENSP00000370512	P1
GTF3A	ENST00000381140.10 linkuse as main transcript	c.*117G>A		3_prime_UTR_variant	9/9	1	NM_002097.3	ENSP00000370532	P1	Q92664-1

Frequencies

GnomAD3 genomes

AF:

0.149

AC:

22665

AN:

151976

Hom.:

1911

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0869

Gnomad AMI

AF:

0.139

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.141

Gnomad SAS

AF:

0.0927

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.165

GnomAD3 exomes

AF:

0.154

AC:

38592

AN:

251372

Hom.:

3415

AF XY:

0.154

AC XY:

20891

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.0876

Gnomad AMR exome

AF:

0.0815

Gnomad ASJ exome

AF:

0.135

Gnomad EAS exome

AF:

0.141

Gnomad SAS exome

AF:

0.0923

Gnomad FIN exome

AF:

0.235

Gnomad NFE exome

AF:

0.190

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.171

AC:

250071

AN:

1461078

Hom.:

22594

Cov.:

AF XY:

0.169

AC XY:

123045

AN XY:

726894

show subpopulations

Gnomad4 AFR exome

AF:

0.0858

Gnomad4 AMR exome

AF:

0.0862

Gnomad4 ASJ exome

AF:

0.133

Gnomad4 EAS exome

AF:

0.146

Gnomad4 SAS exome

AF:

0.0942

Gnomad4 FIN exome

AF:

0.233

Gnomad4 NFE exome

AF:

0.183

Gnomad4 OTH exome

AF:

0.156

GnomAD4 genome

AF:

0.149

AC:

22672

AN:

152094

Hom.:

1911

Cov.:

AF XY:

0.150

AC XY:

11147

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0869

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.129

Gnomad4 EAS

AF:

0.141

Gnomad4 SAS

AF:

0.0924

Gnomad4 FIN

AF:

0.240

Gnomad4 NFE

AF:

0.185

Gnomad4 OTH

AF:

0.167

Alfa

AF:

0.161

Hom.:

1383

Bravo

AF:

0.137

Asia WGS

AF:

0.118

AC:

411

AN:

3478

EpiCase

AF:

0.180

EpiControl

AF:

0.182

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.16

DANN

Benign

0.29

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over