15-65002962-C-CAAA

Variant names:

• chr15-65002962-C-CAAA
• rs398027674
• NM_139242.4:c.*97_*99dupTTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_139242.4(MTFMT):​c.*97_*99dupTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0023 (2 hom., cov: 0)
  • Exomes 𝑓: 0.019 (2 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), Ambry Genetics, G2P
• Leigh syndrome

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.*97_*99dupTTT		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.*97_*99dupTTT		3_prime_UTR	Exon 9 of 9	ENSP00000220058.4	Q96DP5-1
	MTFMT	ENST00000901062.1		c.*97_*99dupTTT		3_prime_UTR	Exon 10 of 10	ENSP00000571121.1
	MTFMT	ENST00000901059.1		c.*97_*99dupTTT		3_prime_UTR	Exon 9 of 9	ENSP00000571118.1

Frequencies

GnomAD3 genomes AF: 0.00225 AC: 135 AN: 59988 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00112

Gnomad AMI AF: 0.00579

Gnomad AMR AF: 0.00120

Gnomad ASJ AF: 0.00168

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00175

Gnomad FIN AF: 0.00200

Gnomad MID AF: 0.00943

Gnomad NFE AF: 0.00305

Gnomad OTH AF: 0.00132

GnomAD4 exome AF: 0.0190 AC: 4999 AN: 262434 Hom.: 2 Cov.: 2 AF XY: 0.0192 AC XY: 2563 AN XY: 133202

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0113 AC: 74 AN: 6574

American (AMR) AF: 0.0184 AC: 107 AN: 5828

Ashkenazi Jewish (ASJ) AF: 0.0197 AC: 110 AN: 5570

East Asian (EAS) AF: 0.00516 AC: 79 AN: 15320

South Asian (SAS) AF: 0.0196 AC: 197 AN: 10076

European-Finnish (FIN) AF: 0.0192 AC: 243 AN: 12628

Middle Eastern (MID) AF: 0.0203 AC: 21 AN: 1032

European-Non Finnish (NFE) AF: 0.0205 AC: 3943 AN: 192368

Other (OTH) AF: 0.0173 AC: 225 AN: 13038

⚠️ 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 AF: 0.00225 AC: 135 AN: 59970 Hom.: 2 Cov.: 0 AF XY: 0.00217 AC XY: 59 AN XY: 27130

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00112 AC: 16 AN: 14312

American (AMR) AF: 0.00120 AC: 6 AN: 4996

Ashkenazi Jewish (ASJ) AF: 0.00168 AC: 3 AN: 1784

East Asian (EAS) AF: 0.00 AC: 0 AN: 1822

South Asian (SAS) AF: 0.00176 AC: 3 AN: 1708

European-Finnish (FIN) AF: 0.00200 AC: 3 AN: 1498

Middle Eastern (MID) AF: 0.0109 AC: 1 AN: 92

European-Non Finnish (NFE) AF: 0.00305 AC: 99 AN: 32482

Other (OTH) AF: 0.00132 AC: 1 AN: 758

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs398027674;

hg19: chr15-65295300;