8-142727818-A-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_016647.3(THEM6):c.472A>T(p.Thr158Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,462,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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. T158I) has been classified as Uncertain significance.
Frequency
Consequence
NM_016647.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THEM6 | NM_016647.3 | c.472A>T | p.Thr158Ser | missense_variant | 1/2 | ENST00000336138.4 | |
THEM6 | NM_001363000.2 | c.354+118A>T | intron_variant | ||||
THEM6 | NR_156431.2 | n.596A>T | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THEM6 | ENST00000336138.4 | c.472A>T | p.Thr158Ser | missense_variant | 1/2 | 1 | NM_016647.3 | P1 | |
THEM6 | ENST00000520217.1 | c.97A>T | p.Thr33Ser | missense_variant, NMD_transcript_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152008Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000174 AC: 1AN: 57508Hom.: 0 AF XY: 0.0000304 AC XY: 1AN XY: 32848
GnomAD4 exome AF: 0.00000687 AC: 9AN: 1310048Hom.: 0 Cov.: 34 AF XY: 0.00000777 AC XY: 5AN XY: 643638
GnomAD4 genome AF: 0.0000789 AC: 12AN: 152008Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74260
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 24, 2022 | The c.472A>T (p.T158S) alteration is located in exon 1 (coding exon 1) of the THEM6 gene. This alteration results from a A to T substitution at nucleotide position 472, causing the threonine (T) at amino acid position 158 to be replaced by a serine (S). 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