15-65002962-CAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr15-65002962-C-CAAAAAAAAAAA
• rs398027674
• NM_139242.4:c.*89_*99dupTTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_139242.4(MTFMT):​c.*89_*99dupTTTTTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: MTFMT NM_139242.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.893
• Publications: 0 publications found

Genes affected

MTFMT (HGNC:29666): (mitochondrial methionyl-tRNA formyltransferase) The protein encoded by this nuclear gene localizes to the mitochondrion, where it catalyzes the formylation of methionyl-tRNA. [provided by RefSeq, Jun 2011]

MTFMT Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation defect type 15

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Leigh syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Leigh syndrome with leukodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139242.4. 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
	MTFMT	NM_139242.4	MANE Select	c.*89_*99dupTTTTTTTTTTT		3_prime_UTR	Exon 9 of 9	NP_640335.2	Q96DP5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTFMT	ENST00000220058.9	TSL:1 MANE Select	c.*89_*99dupTTTTTTTTTTT		3_prime_UTR	Exon 9 of 9	ENSP00000220058.4	Q96DP5-1
	MTFMT	ENST00000901062.1		c.*89_*99dupTTTTTTTTTTT		3_prime_UTR	Exon 10 of 10	ENSP00000571121.1
	MTFMT	ENST00000901059.1		c.*89_*99dupTTTTTTTTTTT		3_prime_UTR	Exon 9 of 9	ENSP00000571118.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000377 AC: 1 AN: 264998 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 134524

⚠️ 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: 6634

American (AMR) AF: 0.00 AC: 0 AN: 5878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5620

East Asian (EAS) AF: 0.00 AC: 0 AN: 15418

South Asian (SAS) AF: 0.00 AC: 0 AN: 10124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12770

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1046

European-Non Finnish (NFE) AF: 0.00000515 AC: 1 AN: 194320

Other (OTH) AF: 0.00 AC: 0 AN: 13188

⚠️ 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.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.89

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs398027674; hg19: chr15-65295300;