Menu
GeneBe

5-134887831-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1

The NM_024715.4(TXNDC15):c.240G>A(p.Ala80=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000691 in 1,614,186 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 Benign (★).

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00069 ( 0 hom. )

Consequence

TXNDC15
NM_024715.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.38
Variant links:
Genes affected
TXNDC15 (HGNC:20652): (thioredoxin domain containing 15) This gene encodes a member of the thioredoxin superfamily. Members of this family are characterized by a conserved active motif called the thioredoxin fold that catalyzes disulfide bond formation and isomerization. [provided by RefSeq, Apr 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-134887831-G-A is Benign according to our data. Variant chr5-134887831-G-A is described in ClinVar as [Benign]. Clinvar id is 1626522.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-4.38 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000729 (111/152300) while in subpopulation NFE AF= 0.00122 (83/68020). AF 95% confidence interval is 0.00101. There are 0 homozygotes in gnomad4. There are 44 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TXNDC15NM_024715.4 linkuse as main transcriptc.240G>A p.Ala80= synonymous_variant 2/5 ENST00000358387.9
TXNDC15NM_001350735.2 linkuse as main transcriptc.36G>A p.Ala12= synonymous_variant 2/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TXNDC15ENST00000358387.9 linkuse as main transcriptc.240G>A p.Ala80= synonymous_variant 2/51 NM_024715.4 P1Q96J42-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000729
AC:
111
AN:
152182
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00259
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00122
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000557
AC:
140
AN:
251396
Hom.:
0
AF XY:
0.000552
AC XY:
75
AN XY:
135886
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.000463
Gnomad ASJ exome
AF:
0.00258
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000792
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000687
AC:
1004
AN:
1461886
Hom.:
0
Cov.:
31
AF XY:
0.000715
AC XY:
520
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.000492
Gnomad4 ASJ exome
AF:
0.00245
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000766
Gnomad4 OTH exome
AF:
0.000679
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000729
AC:
111
AN:
152300
Hom.:
0
Cov.:
33
AF XY:
0.000591
AC XY:
44
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.000192
Gnomad4 AMR
AF:
0.000457
Gnomad4 ASJ
AF:
0.00259
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00122
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000889
Hom.:
0
Bravo
AF:
0.000642
EpiCase
AF:
0.000873
EpiControl
AF:
0.00101

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 17, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
0.43
Dann
Benign
0.68
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6

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: rs143218475; hg19: chr5-134223521; COSMIC: COSV100613684; COSMIC: COSV100613684; API