Variant rs28759013 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -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. 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_001160047.2 splice_acceptor, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.86

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:

TXNDC16 (HGNC:):

TXNDC16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.043036945 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNDC16	NM_020784.3 linkuse as main transcript	c.407G>A	p.Ser136Asn	missense_variant	7/21	ENST00000281741.9	NP_065835.2	Q9P2K2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TXNDC16	ENST00000281741.9 linkuse as main transcript	c.407G>A	p.Ser136Asn	missense_variant	7/21	1	NM_020784.3	ENSP00000281741.4	Q9P2K2
TXNDC16	ENST00000557374.1 linkuse as main transcript	c.-294-28274G>A		intron_variant		4		ENSP00000450839.1	G3V2S5
TXNDC16	ENST00000554399.1 linkuse as main transcript	n.207+33037G>A		intron_variant		4

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

GnomAD3 exomes

AF:

0.00877

AC:

2165

AN:

247004

Hom.:

105

AF XY:

0.00626

AC XY:

837

AN XY:

133648

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 SAS exome

AF:

0.000271

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

Gnomad4 AFR exome

AF:

0.120

Gnomad4 AMR exome

AF:

0.00731

Gnomad4 ASJ exome

AF:

0.0000773

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000319

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000195

Gnomad4 OTH exome

AF:

0.00727

GnomAD4 genome

AF:

0.0346

AC:

5261

AN:

152090

Hom.:

269

Cov.:

AF XY:

0.0331

AC XY:

2460

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.0150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.0279

Alfa

AF:

0.00589

Hom.:

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over