4-82918221-C-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_024672.6(THAP9):c.2009C>A(p.Ala670Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,614,130 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. A670V) has been classified as Uncertain significance.
Frequency
Consequence
NM_024672.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THAP9 | NM_024672.6 | c.2009C>A | p.Ala670Glu | missense_variant | 5/5 | ENST00000302236.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THAP9 | ENST00000302236.10 | c.2009C>A | p.Ala670Glu | missense_variant | 5/5 | 1 | NM_024672.6 | P1 | |
THAP9 | ENST00000505901.1 | c.*1766C>A | 3_prime_UTR_variant, NMD_transcript_variant | 6/6 | 2 | ||||
LIN54 | ENST00000505905.1 | n.305-4780G>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.000493 AC: 75AN: 152166Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000187 AC: 47AN: 251350Hom.: 0 AF XY: 0.000169 AC XY: 23AN XY: 135840
GnomAD4 exome AF: 0.000101 AC: 147AN: 1461846Hom.: 1 Cov.: 67 AF XY: 0.0000880 AC XY: 64AN XY: 727222
GnomAD4 genome AF: 0.000493 AC: 75AN: 152284Hom.: 0 Cov.: 33 AF XY: 0.000416 AC XY: 31AN XY: 74470
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 25, 2023 | The c.2009C>A (p.A670E) alteration is located in exon 5 (coding exon 5) of the THAP9 gene. This alteration results from a C to A substitution at nucleotide position 2009, causing the alanine (A) at amino acid position 670 to be replaced by a glutamic acid (E). 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