5-134874512-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_024715.4(TXNDC15):c.85C>G(p.Pro29Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000225 in 1,601,902 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

TXNDC15
NM_024715.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0071561635).

BP6

Variant 5-134874512-C-G is Benign according to our data. Variant chr5-134874512-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3045423.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00127 (193/152342) while in subpopulation AFR AF = 0.0044 (183/41582). AF 95% confidence interval is 0.00388. There are 0 homozygotes in GnomAd4. There are 90 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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>G	p.Pro29Ala	missense	Exon 1 of 5	NP_078991.3
	TXNDC15	NM_001350735.2		c.-102+29C>G		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>G	p.Pro29Ala	missense	Exon 1 of 5	ENSP00000351157.5	Q96J42-1
TXNDC15	ENST00000511070.5	TSL:1	n.85C>G		non_coding_transcript_exon	Exon 1 of 4	ENSP00000423609.1	D6R962
TXNDC15	ENST00000507024.5	TSL:1	n.56+29C>G		intron	N/A	ENSP00000424716.1	D6RAV9

Frequencies

GnomAD3 genomes

AF:

0.00127

AC:

193

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00441

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000255

AC:

AN:

231048

AF XY:

0.000166

show subpopulations

Gnomad AFR exome

AF:

0.00408

Gnomad AMR exome

AF:

0.0000887

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000175

GnomAD4 exome

AF:

0.000116

AC:

168

AN:

1449560

Hom.:

Cov.:

AF XY:

0.0000998

AC XY:

AN XY:

721472

show subpopulations

African (AFR)

AF:

0.00429

AC:

135

AN:

31492

American (AMR)

AF:

0.0000903

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:

0.0000171

AC:

AN:

1108802

Other (OTH)

AF:

0.000167

AC:

AN:

60026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.00127

AC:

193

AN:

152342

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00440

AC:

183

AN:

41582

American (AMR)

AF:

0.000392

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000201

Hom.:

Bravo

AF:

0.00152

ESP6500AA

AF:

0.00386

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000322

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3474

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

TXNDC15-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.017

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.58

M_CAP

Benign

0.035

MetaRNN

Benign

0.0072

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

1.2

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.10

REVEL

Benign

0.13

Sift

Benign

0.057

Sift4G

Benign

0.30

Polyphen

0.46

Vest4

0.24

MVP

0.43

MPC

0.40

ClinPred

0.058

GERP RS

4.7

PromoterAI

-0.11

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.087

gMVP

0.25

Mutation Taster

=80/20

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over