rs7669

chr13-27435714-G-Achr13-27435714-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336

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]

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]

ACMG classification

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	UniProt
MTIF3	NM_152912.5	c.798C>T	p.Asp266=	synonymous_variant	5/5	ENST00000381120.8
GTF3A	NM_002097.3	c.*117G>A		3_prime_UTR_variant	9/9	ENST00000381140.10

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22665 AN: 151976 Hom.: 1911 Cov.: 33

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

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.: 34 AF XY: 0.169 AC XY: 123045 AN XY: 726894

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.: 33 AF XY: 0.150 AC XY: 11147 AN XY: 74326

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

Other links and lift over

dbSNP: rs7669; hg19: chr13-28009851; COSMIC: COSV63528711; COSMIC: COSV63528711;