Genetic Variant MTFMT:c.*97_*99dupTTT (chr15-65002962-C-CAAA) – ACMG Classification: Likely_benign (-4 pts)

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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.893

Publications

0 publications found

Variant links:

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

MTFMT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	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.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0192

AC XY:

2563

AN XY:

133202

show subpopulations

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

African (AFR)

AF:

0.0113

AC:

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:

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:

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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.292

Heterozygous variant carriers

473

946

1418

1891

2364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

240

360

480

600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00225

AC:

135

AN:

59970

Hom.:

Cov.:

AF XY:

0.00217

AC XY:

AN XY:

27130

show subpopulations

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

African (AFR)

AF:

0.00112

AC:

AN:

14312

American (AMR)

AF:

0.00120

AC:

AN:

4996

Ashkenazi Jewish (ASJ)

AF:

0.00168

AC:

AN:

1784

East Asian (EAS)

AF:

0.00

AC:

AN:

1822

South Asian (SAS)

AF:

0.00176

AC:

AN:

1708

European-Finnish (FIN)

AF:

0.00200

AC:

AN:

1498

Middle Eastern (MID)

AF:

0.0109

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00305

AC:

AN:

32482

Other (OTH)

AF:

0.00132

AC:

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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.336

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.89

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

15-65002962-CAAAAAAAAAAA-CAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over