rs2277105

Positions:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_030810.5(TXNDC5):​c.1116G>A​(p.Ala372=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,614,088 control chromosomes in the GnomAD database, including 910 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.016 ( 151 hom., cov: 32)
Exomes 𝑓: 0.0094 ( 759 hom. )

Consequence

TXNDC5
NM_030810.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.888
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 Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP7
Synonymous conserved (PhyloP=-0.888 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TXNDC5NM_030810.5 linkuse as main transcriptc.1116G>A p.Ala372= synonymous_variant 9/10 ENST00000379757.9
BLOC1S5-TXNDC5NR_037616.1 linkuse as main transcriptn.1275G>A non_coding_transcript_exon_variant 12/13
TXNDC5NM_001145549.4 linkuse as main transcriptc.792G>A p.Ala264= synonymous_variant 9/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TXNDC5ENST00000379757.9 linkuse as main transcriptc.1116G>A p.Ala372= synonymous_variant 9/101 NM_030810.5 P1Q8NBS9-1
TXNDC5ENST00000473453.2 linkuse as main transcriptc.792G>A p.Ala264= synonymous_variant 9/101 Q8NBS9-2
TXNDC5ENST00000460138.5 linkuse as main transcriptn.894G>A non_coding_transcript_exon_variant 3/42
TXNDC5ENST00000475802.1 linkuse as main transcriptn.410G>A non_coding_transcript_exon_variant 3/42

Frequencies

GnomAD3 genomes
AF:
0.0160
AC:
2439
AN:
152106
Hom.:
150
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00280
Gnomad AMI
AF:
0.0208
Gnomad AMR
AF:
0.0864
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.144
Gnomad SAS
AF:
0.00932
Gnomad FIN
AF:
0.000377
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00207
Gnomad OTH
AF:
0.0225
GnomAD3 exomes
AF:
0.0312
AC:
7849
AN:
251494
Hom.:
557
AF XY:
0.0261
AC XY:
3551
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.00351
Gnomad AMR exome
AF:
0.133
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.149
Gnomad SAS exome
AF:
0.00431
Gnomad FIN exome
AF:
0.000554
Gnomad NFE exome
AF:
0.00126
Gnomad OTH exome
AF:
0.0249
GnomAD4 exome
AF:
0.00945
AC:
13812
AN:
1461864
Hom.:
759
Cov.:
30
AF XY:
0.00877
AC XY:
6380
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00206
Gnomad4 AMR exome
AF:
0.129
Gnomad4 ASJ exome
AF:
0.0000765
Gnomad4 EAS exome
AF:
0.123
Gnomad4 SAS exome
AF:
0.00441
Gnomad4 FIN exome
AF:
0.000449
Gnomad4 NFE exome
AF:
0.00174
Gnomad4 OTH exome
AF:
0.0124
GnomAD4 genome
AF:
0.0161
AC:
2449
AN:
152224
Hom.:
151
Cov.:
32
AF XY:
0.0183
AC XY:
1364
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.00279
Gnomad4 AMR
AF:
0.0868
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.145
Gnomad4 SAS
AF:
0.00953
Gnomad4 FIN
AF:
0.000377
Gnomad4 NFE
AF:
0.00207
Gnomad4 OTH
AF:
0.0227
Alfa
AF:
0.00653
Hom.:
52
Bravo
AF:
0.0240
Asia WGS
AF:
0.0580
AC:
201
AN:
3478
EpiCase
AF:
0.00109
EpiControl
AF:
0.00154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
CADD
Benign
5.6
DANN
Benign
0.88
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs2277105; hg19: chr6-7884652; COSMIC: COSV51660422; COSMIC: COSV51660422; API