NM_005726.6:c.231+1096A>G

Variant names:

• chr12-57784379-A-G
• rs6581155
• NM_005726.6:c.231+1096A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005726.6(TSFM):​c.231+1096A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,112 control chromosomes in the GnomAD database, including 8,788 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (8788 hom., cov: 32)
• Consequence: TSFM NM_005726.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 25 publications found

Genes affected

TSFM (HGNC:12367): (Ts translation elongation factor, mitochondrial) This gene encodes a mitochondrial translation elongation factor. The encoded protein is an enzyme that catalyzes the exchange of guanine nucleotides on the translation elongation factor Tu during the elongation step of mitchondrial protein translation. Mutations in this gene are associated with combined oxidative phosphorylation deficiency-3 syndrome. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Mar 2010]

TSFM Gene-Disease associations (from GenCC):

• fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ENSG00000257921 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.08).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005726.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSFM	NM_005726.6	MANE Select	c.231+1096A>G		intron	N/A	NP_005717.3
	TSFM	NM_001172696.2		c.231+1096A>G		intron	N/A	NP_001166167.1
	TSFM	NM_001172697.2		c.231+1096A>G		intron	N/A	NP_001166168.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSFM	ENST00000652027.2	MANE Select	c.231+1096A>G		intron	N/A	ENSP00000499171.2
	TSFM	ENST00000323833.12	TSL:1	c.231+1096A>G		intron	N/A	ENSP00000313877.8
	TSFM	ENST00000543727.5	TSL:1	c.231+1096A>G		intron	N/A	ENSP00000439342.1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50123 AN: 151994 Hom.: 8761 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.283

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.330 AC: 50203 AN: 152112 Hom.: 8788 Cov.: 32 AF XY: 0.338 AC XY: 25135 AN XY: 74366

African (AFR) AF: 0.289 AC: 11992 AN: 41494

American (AMR) AF: 0.283 AC: 4328 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1031 AN: 3466

East Asian (EAS) AF: 0.655 AC: 3391 AN: 5178

South Asian (SAS) AF: 0.567 AC: 2736 AN: 4822

European-Finnish (FIN) AF: 0.377 AC: 3984 AN: 10566

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21731 AN: 67972

Other (OTH) AF: 0.289 AC: 611 AN: 2114

Alfa AF: 0.313 Hom.: 17752

Bravo AF: 0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.0
DANN	Benign	0.18
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs6581155; hg19: chr12-58178162;