chr14-52470130-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_020784.3(TXNDC16):c.1525G>A(p.Ala509Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000683 in 1,610,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
TXNDC16
NM_020784.3 missense
NM_020784.3 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 3.73
Genes affected
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.20012265).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TXNDC16 | NM_020784.3 | c.1525G>A | p.Ala509Thr | missense_variant | 16/21 | ENST00000281741.9 | |
TXNDC16 | NM_001160047.2 | c.1510G>A | p.Ala504Thr | missense_variant | 16/21 | ||
TXNDC16 | XR_007064037.1 | n.1896G>A | non_coding_transcript_exon_variant | 16/19 | |||
TXNDC16 | XR_007064038.1 | n.1896G>A | non_coding_transcript_exon_variant | 16/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TXNDC16 | ENST00000281741.9 | c.1525G>A | p.Ala509Thr | missense_variant | 16/21 | 1 | NM_020784.3 | P1 | |
TXNDC16 | ENST00000555312.1 | c.208G>A | p.Ala70Thr | missense_variant, NMD_transcript_variant | 2/5 | 5 | |||
TXNDC16 | ENST00000554399.1 | n.208-29406G>A | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152064Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000240 AC: 6AN: 250454Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135440
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GnomAD4 exome AF: 0.00000617 AC: 9AN: 1458802Hom.: 0 Cov.: 30 AF XY: 0.00000689 AC XY: 5AN XY: 725814
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152064Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74272
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 20, 2022 | The c.1525G>A (p.A509T) alteration is located in exon 16 (coding exon 14) of the TXNDC16 gene. This alteration results from a G to A substitution at nucleotide position 1525, causing the alanine (A) at amino acid position 509 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Gain of catalytic residue at A509 (P = 0.0696);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at