15-65002962-CAAAAAAAAAAA-CAAAAAAAAAA

Variant names:

• chr15-65002962-CA-C
• rs398027674
• NM_139242.4:c.*99delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_139242.4(MTFMT):​c.*99delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (5 hom., cov: 0)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: MTFMT NM_139242.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 15-65002962-CA-C is Benign according to our data. Variant chr15-65002962-CA-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1205642.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.016 (972/60720) while in subpopulation AFR AF = 0.0376 (541/14380). AF 95% confidence interval is 0.035. There are 5 homozygotes in GnomAd4. There are 459 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 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.*99delT		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.*99delT		3_prime_UTR	Exon 9 of 9	ENSP00000220058.4	Q96DP5-1
	MTFMT	ENST00000901062.1		c.*99delT		3_prime_UTR	Exon 10 of 10	ENSP00000571121.1
	MTFMT	ENST00000901059.1		c.*99delT		3_prime_UTR	Exon 9 of 9	ENSP00000571118.1

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 963 AN: 60738 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.0878

Gnomad AMR AF: 0.0193

Gnomad ASJ AF: 0.00221

Gnomad EAS AF: 0.00490

Gnomad SAS AF: 0.00696

Gnomad FIN AF: 0.00334

Gnomad MID AF: 0.0185

Gnomad NFE AF: 0.00737

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.104 AC: 27229 AN: 262120 Hom.: 0 Cov.: 2 AF XY: 0.104 AC XY: 13796 AN XY: 133020

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

African (AFR) AF: 0.136 AC: 895 AN: 6574

American (AMR) AF: 0.120 AC: 697 AN: 5794

Ashkenazi Jewish (ASJ) AF: 0.0999 AC: 555 AN: 5554

East Asian (EAS) AF: 0.156 AC: 2374 AN: 15204

South Asian (SAS) AF: 0.106 AC: 1066 AN: 10030

European-Finnish (FIN) AF: 0.0991 AC: 1249 AN: 12602

Middle Eastern (MID) AF: 0.115 AC: 119 AN: 1032

European-Non Finnish (NFE) AF: 0.0982 AC: 18883 AN: 192288

Other (OTH) AF: 0.107 AC: 1391 AN: 13042

⚠️ 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: 0.0160 AC: 972 AN: 60720 Hom.: 5 Cov.: 0 AF XY: 0.0167 AC XY: 459 AN XY: 27448

African (AFR) AF: 0.0376 AC: 541 AN: 14380

American (AMR) AF: 0.0193 AC: 97 AN: 5018

Ashkenazi Jewish (ASJ) AF: 0.00221 AC: 4 AN: 1806

East Asian (EAS) AF: 0.00492 AC: 9 AN: 1830

South Asian (SAS) AF: 0.00698 AC: 12 AN: 1718

European-Finnish (FIN) AF: 0.00334 AC: 5 AN: 1498

Middle Eastern (MID) AF: 0.0213 AC: 2 AN: 94

European-Non Finnish (NFE) AF: 0.00737 AC: 244 AN: 33090

Other (OTH) AF: 0.0157 AC: 12 AN: 762

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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

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: rs398027674; hg19: chr15-65295300;