12-29516356-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001193451.2(TMTC1):āc.2300A>Gā(p.His767Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000391 in 1,613,156 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H767Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_001193451.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMTC1 | NM_001193451.2 | c.2300A>G | p.His767Arg | missense_variant | 15/18 | ENST00000539277.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMTC1 | ENST00000539277.6 | c.2300A>G | p.His767Arg | missense_variant | 15/18 | 1 | NM_001193451.2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152116Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250926Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135600
GnomAD4 exome AF: 0.0000411 AC: 60AN: 1461040Hom.: 0 Cov.: 30 AF XY: 0.0000413 AC XY: 30AN XY: 726764
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152116Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74278
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 14, 2023 | The c.2300A>G (p.H767R) alteration is located in exon 15 (coding exon 15) of the TMTC1 gene. This alteration results from a A to G substitution at nucleotide position 2300, causing the histidine (H) at amino acid position 767 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at