Genetic Variant TXNDC15:p.Pro29Ser (chr5-134874512-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024715.4(TXNDC15):c.85C>T(p.Pro29Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P29A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TXNDC15
NM_024715.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.19

Publications

0 publications found

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]

TXNDC15 Gene-Disease associations (from GenCC):

ciliopathy
Inheritance: AR Classification: STRONG Submitted by: ClinGen
meckel syndrome 14
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Meckel syndrome
Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet

TXNDC15 links:

ENSG00000300583 (HGNC:):

ENSG00000300583 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23801994).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024715.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC15	NM_024715.4	MANE Select	c.85C>T	p.Pro29Ser	missense	Exon 1 of 5	NP_078991.3
	TXNDC15	NM_001350735.2		c.-102+29C>T		intron	N/A	NP_001337664.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TXNDC15	ENST00000358387.9	TSL:1 MANE Select	c.85C>T	p.Pro29Ser	missense	Exon 1 of 5	ENSP00000351157.5	Q96J42-1
TXNDC15	ENST00000511070.5	TSL:1	n.85C>T		non_coding_transcript_exon	Exon 1 of 4	ENSP00000423609.1	D6R962
TXNDC15	ENST00000507024.5	TSL:1	n.56+29C>T		intron	N/A	ENSP00000424716.1	D6RAV9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449560

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721470

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31494

American (AMR)

AF:

0.00

AC:

AN:

44294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25650

East Asian (EAS)

AF:

0.00

AC:

AN:

38308

South Asian (SAS)

AF:

0.00

AC:

AN:

85600

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49654

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108800

Other (OTH)

AF:

0.00

AC:

AN:

60026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.010

Eigen

Benign

-0.045

Eigen_PC

Benign

-0.023

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.51

M_CAP

Benign

0.051

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PhyloP100

1.2

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.56

REVEL

Benign

0.11

Sift

Benign

0.097

Sift4G

Benign

0.14

Polyphen

0.86

Vest4

0.13

MutPred

0.48

Gain of sheet (P = 0.0344)

MVP

0.55

MPC

0.64

ClinPred

0.68

GERP RS

4.7

PromoterAI

-0.11

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.098

gMVP

0.31

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over