19-3053974-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001130.6(TLE5):c.439G>A(p.Val147Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,610,176 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 (★).
Frequency
Consequence
NM_001130.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TLE5 | NM_001130.6 | c.439G>A | p.Val147Met | missense_variant | 7/7 | ENST00000327141.9 | NP_001121.2 | |
TLE5 | NM_198969.1 | c.640G>A | p.Val214Met | missense_variant | 7/7 | NP_945320.1 | ||
TLE5 | NM_198970.2 | c.436G>A | p.Val146Met | missense_variant | 7/7 | NP_945321.1 | ||
TLE5 | XM_006722664.2 | c.637G>A | p.Val213Met | missense_variant | 7/7 | XP_006722727.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152148Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000719 AC: 17AN: 236284Hom.: 0 AF XY: 0.0000769 AC XY: 10AN XY: 130120
GnomAD4 exome AF: 0.000155 AC: 226AN: 1458028Hom.: 0 Cov.: 41 AF XY: 0.000142 AC XY: 103AN XY: 725206
GnomAD4 genome AF: 0.0000789 AC: 12AN: 152148Hom.: 0 Cov.: 34 AF XY: 0.0000807 AC XY: 6AN XY: 74316
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 25, 2023 | The c.640G>A (p.V214M) alteration is located in exon 7 (coding exon 7) of the AES gene. This alteration results from a G to A substitution at nucleotide position 640, causing the valine (V) at amino acid position 214 to be replaced by a methionine (M). 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