rs7669

Variant names:

• chr13-27435714-G-A
• rs7669
• NM_152912.5:c.798C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-27435714-G-A
• chr13-27435714-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_152912.5(MTIF3):​c.798C>T​(p.Asp266Asp) 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
• Publications: 24 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152912.5. 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
	MTIF3	NM_152912.5	MANE Select	c.798C>T	p.Asp266Asp	synonymous	Exon 5 of 5	NP_690876.3
	GTF3A	NM_002097.3	MANE Select	c.*117G>A		3_prime_UTR	Exon 9 of 9	NP_002088.2	Q92664-1
	MTIF3	NM_001166261.2		c.798C>T	p.Asp266Asp	synonymous	Exon 5 of 5	NP_001159733.1	Q9H2K0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTIF3	ENST00000381120.8	TSL:1 MANE Select	c.798C>T	p.Asp266Asp	synonymous	Exon 5 of 5	ENSP00000370512.3	Q9H2K0
	MTIF3	ENST00000405591.3	TSL:1	c.798C>T	p.Asp266Asp	synonymous	Exon 3 of 3	ENSP00000384659.2	Q9H2K0
	GTF3A	ENST00000381140.10	TSL:1 MANE Select	c.*117G>A		3_prime_UTR	Exon 9 of 9	ENSP00000370532.5	Q92664-1

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

GnomAD2 exomes AF: 0.154 AC: 38592 AN: 251372 AF XY: 0.154

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 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

African (AFR) AF: 0.0858 AC: 2873 AN: 33474

American (AMR) AF: 0.0862 AC: 3855 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 3466 AN: 26128

East Asian (EAS) AF: 0.146 AC: 5785 AN: 39696

South Asian (SAS) AF: 0.0942 AC: 8123 AN: 86240

European-Finnish (FIN) AF: 0.233 AC: 12439 AN: 53372

Middle Eastern (MID) AF: 0.120 AC: 690 AN: 5762

European-Non Finnish (NFE) AF: 0.183 AC: 203412 AN: 1111320

Other (OTH) AF: 0.156 AC: 9428 AN: 60364

GnomAD4 genome AF: 0.149 AC: 22672 AN: 152094 Hom.: 1911 Cov.: 33 AF XY: 0.150 AC XY: 11147 AN XY: 74326

African (AFR) AF: 0.0869 AC: 3605 AN: 41492

American (AMR) AF: 0.119 AC: 1818 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 448 AN: 3472

East Asian (EAS) AF: 0.141 AC: 729 AN: 5174

South Asian (SAS) AF: 0.0924 AC: 445 AN: 4818

European-Finnish (FIN) AF: 0.240 AC: 2533 AN: 10550

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12589 AN: 67980

Other (OTH) AF: 0.167 AC: 352 AN: 2110

Alfa AF: 0.160 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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.16
DANN	Benign	0.29
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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