chr14-61280814-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001017970.3(TMEM30B):c.334T>C(p.Tyr112His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000102 in 1,564,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y112D) has been classified as Uncertain significance.
Frequency
Consequence
NM_001017970.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM30B | NM_001017970.3 | c.334T>C | p.Tyr112His | missense_variant | 1/1 | ENST00000555868.2 | |
PRKCH | XM_024449661.2 | c.-121+93146A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM30B | ENST00000555868.2 | c.334T>C | p.Tyr112His | missense_variant | 1/1 | NM_001017970.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152126Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000526 AC: 1AN: 190258Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 104060
GnomAD4 exome AF: 0.0000106 AC: 15AN: 1412474Hom.: 0 Cov.: 29 AF XY: 0.0000114 AC XY: 8AN XY: 699666
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152126Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74336
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 27, 2022 | The c.334T>C (p.Y112H) alteration is located in exon 1 (coding exon 1) of the TMEM30B gene. This alteration results from a T to C substitution at nucleotide position 334, causing the tyrosine (Y) at amino acid position 112 to be replaced by a histidine (H). 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