chr6-7884388-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_030810.5(TXNDC5):ā€‹c.1147G>Cā€‹(p.Ala383Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

TXNDC5
NM_030810.5 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.58
Variant links:
Genes affected
TXNDC5 (HGNC:21073): (thioredoxin domain containing 5) This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal endoplasmic reticulum (ER)-signal sequence, three catalytically active thioredoxin domains and a C-terminal ER-retention sequence. Its expression is induced by hypoxia and its role may be to protect hypoxic cells from apoptosis. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring upstream BLOC1S5 gene. [provided by RefSeq, Dec 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.385008).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TXNDC5NM_030810.5 linkuse as main transcriptc.1147G>C p.Ala383Pro missense_variant 9/10 ENST00000379757.9
BLOC1S5-TXNDC5NR_037616.1 linkuse as main transcriptn.1306G>C non_coding_transcript_exon_variant 12/13
TXNDC5NM_001145549.4 linkuse as main transcriptc.823G>C p.Ala275Pro missense_variant 9/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TXNDC5ENST00000379757.9 linkuse as main transcriptc.1147G>C p.Ala383Pro missense_variant 9/101 NM_030810.5 P1Q8NBS9-1
TXNDC5ENST00000473453.2 linkuse as main transcriptc.823G>C p.Ala275Pro missense_variant 9/101 Q8NBS9-2
TXNDC5ENST00000460138.5 linkuse as main transcriptn.925G>C non_coding_transcript_exon_variant 3/42
TXNDC5ENST00000475802.1 linkuse as main transcriptn.441G>C non_coding_transcript_exon_variant 3/42

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251484
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461858
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsMar 21, 2023The c.1147G>C (p.A383P) alteration is located in exon 9 (coding exon 9) of the TXNDC5 gene. This alteration results from a G to C substitution at nucleotide position 1147, causing the alanine (A) at amino acid position 383 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.60
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.17
T;.
Eigen
Benign
0.16
Eigen_PC
Benign
0.054
FATHMM_MKL
Benign
0.41
N
LIST_S2
Uncertain
0.96
D;D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.39
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
2.0
M;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.39
T
PROVEAN
Uncertain
-2.7
D;D
REVEL
Benign
0.18
Sift
Benign
0.069
T;T
Sift4G
Benign
0.20
T;T
Polyphen
0.78
P;.
Vest4
0.45
MutPred
0.57
Gain of phosphorylation at T382 (P = 0.0792);.;
MVP
0.26
MPC
0.51
ClinPred
0.90
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.83
gMVP
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1410494618; hg19: chr6-7884621; API