rs61734099
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_017866.6(TMEM70):āc.379A>Gā(p.Thr127Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00831 in 1,614,150 control chromosomes in the GnomAD database, including 1,258 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T127R) has been classified as Uncertain significance.
Frequency
Consequence
NM_017866.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM70 | NM_017866.6 | c.379A>G | p.Thr127Ala | missense_variant | 3/3 | ENST00000312184.6 | |
TMEM70 | NM_001040613.3 | c.*69A>G | 3_prime_UTR_variant | 3/3 | |||
TMEM70 | NR_033334.2 | n.559A>G | non_coding_transcript_exon_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM70 | ENST00000312184.6 | c.379A>G | p.Thr127Ala | missense_variant | 3/3 | 1 | NM_017866.6 | P1 | |
TMEM70 | ENST00000517439.1 | c.*69A>G | 3_prime_UTR_variant | 3/3 | 2 | ||||
TMEM70 | ENST00000519551.1 | n.270A>G | non_coding_transcript_exon_variant | 3/3 | 2 | ||||
TMEM70 | ENST00000416961.6 | c.*136A>G | 3_prime_UTR_variant, NMD_transcript_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0150 AC: 2285AN: 152186Hom.: 208 Cov.: 33
GnomAD3 exomes AF: 0.0324 AC: 8133AN: 251396Hom.: 850 AF XY: 0.0254 AC XY: 3447AN XY: 135874
GnomAD4 exome AF: 0.00760 AC: 11115AN: 1461846Hom.: 1047 Cov.: 33 AF XY: 0.00685 AC XY: 4981AN XY: 727226
GnomAD4 genome ? AF: 0.0151 AC: 2298AN: 152304Hom.: 211 Cov.: 33 AF XY: 0.0177 AC XY: 1316AN XY: 74472
ClinVar
Submissions by phenotype
Mitochondrial complex V (ATP synthase) deficiency nuclear type 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 27, 2014 | 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. - |
not provided Benign:1
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 23, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at