12-57782794-C-T

Variant names:

• chr12-57782794-C-T
• rs983238298
• NM_005726.6:c.-8C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005726.6(TSFM):​c.-8C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TSFM NM_005726.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Orphanet
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ENSG00000257921 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.-8C>T		5_prime_UTR	Exon 1 of 6	NP_005717.3
	TSFM	NM_001172696.2		c.-8C>T		5_prime_UTR	Exon 1 of 7	NP_001166167.1	P43897-2
	TSFM	NM_001172697.2		c.-8C>T		5_prime_UTR	Exon 1 of 6	NP_001166168.1	P43897-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSFM	ENST00000652027.2	MANE Select	c.-8C>T		5_prime_UTR	Exon 1 of 6	ENSP00000499171.2	P43897-1
	TSFM	ENST00000323833.12	TSL:1	c.-8C>T		5_prime_UTR	Exon 1 of 7	ENSP00000313877.8	P43897-2
	ENSG00000257921	ENST00000546504.1	TSL:2	c.77-316C>T		intron	N/A	ENSP00000449544.1	H0YIJ7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1434866 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 711138

African (AFR) AF: 0.00 AC: 0 AN: 32886

American (AMR) AF: 0.00 AC: 0 AN: 40606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25606

East Asian (EAS) AF: 0.00 AC: 0 AN: 38034

South Asian (SAS) AF: 0.00 AC: 0 AN: 82130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099422

Other (OTH) AF: 0.00 AC: 0 AN: 59340

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		0.22
PromoterAI		-0.091	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs983238298; hg19: chr12-58176577;