NM_005726.6:c.231+1082G>A

Variant names:

• chr12-57784365-G-A
• rs10431552
• NM_005726.6:c.231+1082G>A

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+1082G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,116 control chromosomes in the GnomAD database, including 7,151 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 0.28 (7151 hom., cov: 33)
• Consequence: TSFM NM_005726.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.584
• Publications: 28 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):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.637 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSFM	NM_005726.6	MANE Select	c.231+1082G>A		intron	N/A	NP_005717.3
	TSFM	NM_001172696.2		c.231+1082G>A		intron	N/A	NP_001166167.1	P43897-2
	TSFM	NM_001172697.2		c.231+1082G>A		intron	N/A	NP_001166168.1	P43897-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSFM	ENST00000652027.2	MANE Select	c.231+1082G>A		intron	N/A	ENSP00000499171.2	P43897-1
	TSFM	ENST00000323833.12	TSL:1	c.231+1082G>A		intron	N/A	ENSP00000313877.8	P43897-2
	TSFM	ENST00000543727.5	TSL:1	c.231+1082G>A		intron	N/A	ENSP00000439342.1	P43897-4

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42146 AN: 151998 Hom.: 7133 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.277 AC: 42199 AN: 152116 Hom.: 7151 Cov.: 33 AF XY: 0.286 AC XY: 21300 AN XY: 74360

African (AFR) AF: 0.108 AC: 4476 AN: 41532

American (AMR) AF: 0.262 AC: 4000 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 988 AN: 3466

East Asian (EAS) AF: 0.655 AC: 3392 AN: 5176

South Asian (SAS) AF: 0.567 AC: 2732 AN: 4820

European-Finnish (FIN) AF: 0.378 AC: 3989 AN: 10540

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21686 AN: 67974

Other (OTH) AF: 0.256 AC: 541 AN: 2116

Alfa AF: 0.278 Hom.: 9638

Bravo AF: 0.257

Asia WGS AF: 0.593 AC: 2057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.90
DANN	Benign	0.15
PhyloP100		-0.58
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: rs10431552; hg19: chr12-58178148;