15-65003167-C-T

Variant names:

• chr15-65003167-C-T
• rs35477493
• NM_139242.4:c.1065G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_139242.4(MTFMT):​c.1065G>A​(p.Gln355Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 1,613,556 control chromosomes in the GnomAD database, including 1,344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (108 hom., cov: 31)
  • Exomes 𝑓: 0.029 (1236 hom.)
• Consequence: MTFMT NM_139242.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.113

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 Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 15-65003167-C-T is Benign according to our data. Variant chr15-65003167-C-T is described in ClinVar as [Benign]. Clinvar id is 138266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.113 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTFMT	NM_139242.4	c.1065G>A	p.Gln355Gln	synonymous_variant	Exon 9 of 9	ENST00000220058.9	NP_640335.2
MTFMT	XM_005254158.6	c.1218G>A	p.Gln406Gln	synonymous_variant	Exon 9 of 9		XP_005254215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTFMT	ENST00000220058.9	c.1065G>A	p.Gln355Gln	synonymous_variant	Exon 9 of 9	1	NM_139242.4	ENSP00000220058.4
MTFMT	ENST00000558460.5	n.1065G>A		non_coding_transcript_exon_variant	Exon 9 of 10	5		ENSP00000452646.1
MTFMT	ENST00000560717.5	n.*535G>A		non_coding_transcript_exon_variant	Exon 8 of 8	5		ENSP00000457257.1
MTFMT	ENST00000560717.5	n.*535G>A		3_prime_UTR_variant	Exon 8 of 8	5		ENSP00000457257.1

Frequencies

GnomAD3 genomes AF: 0.0276 AC: 4195 AN: 152016 Hom.: 108 Cov.: 31

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0270

Gnomad ASJ AF: 0.0603

Gnomad EAS AF: 0.00829

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0360

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0221

Gnomad OTH AF: 0.0297

GnomAD3 exomes AF: 0.0369 AC: 9178 AN: 248984 Hom.: 394 AF XY: 0.0424 AC XY: 5731 AN XY: 135094

Gnomad AFR exome AF: 0.0221

Gnomad AMR exome AF: 0.0179

Gnomad ASJ exome AF: 0.0628

Gnomad EAS exome AF: 0.00390

Gnomad SAS exome AF: 0.130

Gnomad FIN exome AF: 0.0300

Gnomad NFE exome AF: 0.0239

Gnomad OTH exome AF: 0.0341

GnomAD4 exome AF: 0.0289 AC: 42221 AN: 1461422 Hom.: 1236 Cov.: 32 AF XY: 0.0321 AC XY: 23349 AN XY: 726984

Gnomad4 AFR exome AF: 0.0223

Gnomad4 AMR exome AF: 0.0181

Gnomad4 ASJ exome AF: 0.0631

Gnomad4 EAS exome AF: 0.00262

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.0276

Gnomad4 NFE exome AF: 0.0219

Gnomad4 OTH exome AF: 0.0327

GnomAD4 genome AF: 0.0276 AC: 4199 AN: 152134 Hom.: 108 Cov.: 31 AF XY: 0.0304 AC XY: 2258 AN XY: 74352

Gnomad4 AFR AF: 0.0221

Gnomad4 AMR AF: 0.0268

Gnomad4 ASJ AF: 0.0603

Gnomad4 EAS AF: 0.00831

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.0360

Gnomad4 NFE AF: 0.0221

Gnomad4 OTH AF: 0.0299

Alfa AF: 0.0252 Hom.: 25

Bravo AF: 0.0235

Asia WGS AF: 0.0660 AC: 229 AN: 3478

EpiCase AF: 0.0235

EpiControl AF: 0.0240

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 26, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Sep 09, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.8
DANN	Benign	0.57

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

LitVar

Other links and lift over

dbSNP: rs35477493; hg19: chr15-65295505;