rs1446833139

Variant names:

• chr15-65003169-G-A
• NM_139242.4:c.1063C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-65003169-G-A
• chr15-65003169-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_139242.4(MTFMT):​c.1063C>T​(p.Gln355*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000137 in 1,461,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MTFMT NM_139242.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.72

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0915 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTFMT	NM_139242.4	c.1063C>T	p.Gln355*	stop_gained	Exon 9 of 9	ENST00000220058.9	NP_640335.2
MTFMT	XM_005254158.6	c.1216C>T	p.Gln406*	stop_gained	Exon 9 of 9		XP_005254215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTFMT	ENST00000220058.9	c.1063C>T	p.Gln355*	stop_gained	Exon 9 of 9	1	NM_139242.4	ENSP00000220058.4
MTFMT	ENST00000558460.5	n.1063C>T		non_coding_transcript_exon_variant	Exon 9 of 10	5		ENSP00000452646.1
MTFMT	ENST00000560717.5	n.*533C>T		non_coding_transcript_exon_variant	Exon 8 of 8	5		ENSP00000457257.1
MTFMT	ENST00000560717.5	n.*533C>T		3_prime_UTR_variant	Exon 8 of 8	5		ENSP00000457257.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461446 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727002

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.60
CADD	Pathogenic	37
DANN	Uncertain	0.99
Eigen	Pathogenic	0.77
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.91	D
Vest4		0.22
GERP RS		4.4

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-65295507;