dbSNP rs28759013: TXNDC16:p.Ser136Asn (chr14-52519279-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PVS1_ModerateBA1

The NM_001160047.2(TXNDC16):c.393-1G>A variant causes a splice acceptor, intron 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. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.035 ( 269 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 260 hom. )

Consequence

TXNDC16
NM_001160047.2 splice_acceptor, intron

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: Likely_benign. The variant received -6 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.043442957 fraction of the gene. Cryptic splice site detected, with MaxEntScore 8.6, offset of -15, new splice context is: tatatctgtatttatttcAGtgc. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160047.2. 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
	TXNDC16	NM_020784.3	MANE Select	c.407G>A	p.Ser136Asn	missense	Exon 7 of 21	NP_065835.2
	TXNDC16	NM_001160047.2		c.393-1G>A		splice_acceptor intron	N/A	NP_001153519.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TXNDC16	ENST00000281741.9	TSL:1 MANE Select	c.407G>A	p.Ser136Asn	missense	Exon 7 of 21	ENSP00000281741.4
TXNDC16	ENST00000936707.1		c.407G>A	p.Ser136Asn	missense	Exon 7 of 21	ENSP00000606766.1
TXNDC16	ENST00000956219.1		c.407G>A	p.Ser136Asn	missense	Exon 8 of 22	ENSP00000626278.1

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 v4.9

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

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