Genetic Variant NM_020784.3:c.407G>A (chr14-52519279-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020784.3(TXNDC16):c.407G>A(p.Ser136Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00638 in 1,595,622 control chromosomes in the GnomAD database, including 529 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.035 ( 269 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 260 hom. )

Consequence

TXNDC16
NM_020784.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.86

Publications

8 publications found

Variant links:

Genes affected

TXNDC16 (HGNC:19965): (thioredoxin domain containing 16) Located in endoplasmic reticulum lumen. [provided by Alliance of Genome Resources, Apr 2022]

TXNDC16 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014813244).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNDC16	NM_020784.3 link	c.407G>A	p.Ser136Asn	missense_variant	Exon 7 of 21	ENST00000281741.9	NP_065835.2	Q9P2K2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNDC16	ENST00000281741.9 link	c.407G>A	p.Ser136Asn	missense_variant	Exon 7 of 21	1	NM_020784.3	ENSP00000281741.4		Q9P2K2

Frequencies

GnomAD3 genomes

AF:

0.0345

AC:

5242

AN:

151972

Hom.:

268

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.0282

GnomAD2 exomes

AF:

0.00877

AC:

2165

AN:

247004

AF XY:

0.00626

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.00602

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000356

Gnomad OTH exome

AF:

0.00551

GnomAD4 exome

AF:

0.00341

AC:

4920

AN:

1443532

Hom.:

260

Cov.:

AF XY:

0.00294

AC XY:

2111

AN XY:

718986

show subpopulations

African (AFR)

AF:

0.120

AC:

3891

AN:

32526

American (AMR)

AF:

0.00731

AC:

322

AN:

44026

Ashkenazi Jewish (ASJ)

AF:

0.0000773

AC:

AN:

25866

East Asian (EAS)

AF:

0.00

AC:

AN:

39388

South Asian (SAS)

AF:

0.000319

AC:

AN:

84610

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53150

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

4412

European-Non Finnish (NFE)

AF:

0.000195

AC:

215

AN:

1099998

Other (OTH)

AF:

0.00727

AC:

433

AN:

59556

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.416

Heterozygous variant carriers

190

381

571

762

952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

252

378

504

630

<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:

0.0346

AC:

5261

AN:

152090

Hom.:

269

Cov.:

AF XY:

0.0331

AC XY:

2460

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.119

AC:

4941

AN:

41462

American (AMR)

AF:

0.0150

AC:

229

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000415

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10560

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

68018

Other (OTH)

AF:

0.0279

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

241

481

722

962

1203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0124

Hom.:

214

Bravo

AF:

0.0394

ESP6500AA

AF:

0.117

AC:

514

ESP6500EA

AF:

0.000816

AC:

ExAC

AF:

0.0112

AC:

1363

Asia WGS

AF:

0.00868

AC:

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.40

DEOGEN2

Benign

0.0015

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.5

PhyloP100

3.9

PrimateAI

Uncertain

0.57

PROVEAN

Benign

1.4

REVEL

Benign

0.15

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.21

MPC

0.019

ClinPred

0.0060

GERP RS

5.6

Varity_R

0.053

gMVP

0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over