dbSNP rs1407767113: TXNDC2:p.Ala115Asp (chr18-9887024-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032243.6(TXNDC2):c.344C>A(p.Ala115Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,455,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. A115G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TXNDC2
NM_032243.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.69

Publications

0 publications found

Variant links:

Genes affected

TXNDC2 (HGNC:16470): (thioredoxin domain containing 2) Enables thioredoxin-disulfide reductase activity. Predicted to be involved in cell differentiation and cellular oxidant detoxification. Predicted to act upstream of or within cellular response to reactive oxygen species and flagellated sperm motility. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TXNDC2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06732574).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032243.6. 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
	TXNDC2	NM_032243.6	MANE Select	c.344C>A	p.Ala115Asp	missense	Exon 2 of 2	NP_115619.4
	TXNDC2	NM_001098529.2		c.545C>A	p.Ala182Asp	missense	Exon 2 of 2	NP_001091999.1	A0A140VJY8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TXNDC2	ENST00000357775.6	TSL:1 MANE Select	c.344C>A	p.Ala115Asp	missense	Exon 2 of 2	ENSP00000350419.4	Q86VQ3-2
TXNDC2	ENST00000306084.6	TSL:1	c.545C>A	p.Ala182Asp	missense	Exon 2 of 2	ENSP00000304908.6	Q86VQ3-1
TXNDC2	ENST00000536353.2	TSL:5	c.328+16C>A		intron	N/A	ENSP00000437393.2	F5H6S7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1455692

Hom.:

Cov.:

129

AF XY:

0.00000552

AC XY:

AN XY:

724218

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33200

American (AMR)

AF:

0.00

AC:

AN:

44078

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25870

East Asian (EAS)

AF:

0.00

AC:

AN:

39284

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85770

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00000541

AC:

AN:

1108442

Other (OTH)

AF:

0.00

AC:

AN:

59984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

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

0.15

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.095

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.025

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.30

M_CAP

Benign

0.0046

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

-4.7

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.98

REVEL

Benign

0.029

Sift

Uncertain

0.020

Sift4G

Benign

0.42

Polyphen

0.64

Vest4

0.092

MutPred

0.14

Gain of relative solvent accessibility (P = 0.1571)

MVP

0.32

MPC

0.12

ClinPred

0.18

GERP RS

-1.4

Varity_R

0.11

gMVP

0.030

Mutation Taster

=98/2

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

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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