rs2783175

Variant names:

Variant summary

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

The NM_138417.3(KTI12):c.573T>A(p.Asp191Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0492 in 1,614,150 control chromosomes in the GnomAD database, including 2,308 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.055 ( 285 hom., cov: 33)

Exomes 𝑓: 0.049 ( 2023 hom. )

Consequence

KTI12
NM_138417.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.44

Publications

15 publications found

Variant links:

Genes affected

KTI12 (HGNC:25160): (KTI12 chromatin associated homolog) Predicted to enable ATP binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II and tRNA wobble uridine modification. [provided by Alliance of Genome Resources, Apr 2022]

KTI12 links:

ENSG00000285839 (HGNC:):

ENSG00000285839 links:

TXNDC12 (HGNC:24626): (thioredoxin domain containing 12) 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. This protein localizes to the endoplasmic reticulum and has a single atypical active motif. The encoded protein is mainly involved in catalyzing native disulfide bond formation and displays activity similar to protein-disulfide isomerases. This protein may play a role in defense against endoplasmic reticulum stress. Alternate splicing results in both coding and non-coding variants. [provided by RefSeq, Mar 2012]

TXNDC12 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=0.0013937652).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KTI12	NM_138417.3 link	c.573T>A	p.Asp191Glu	missense_variant	Exon 1 of 1	ENST00000371614.2	NP_612426.1	Q96EK9
TXNDC12	NM_015913.4 link	c.159-4559T>A		intron_variant	Intron 2 of 6	ENST00000371626.9	NP_056997.1	O95881
TXNDC12	NR_046405.1 link	n.2096T>A		non_coding_transcript_exon_variant	Exon 3 of 3
TXNDC12	NR_046406.1 link	n.1973T>A		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KTI12	ENST00000371614.2 link	c.573T>A	p.Asp191Glu	missense_variant	Exon 1 of 1	6	NM_138417.3	ENSP00000360676.1	Q96EK9
ENSG00000285839	ENST00000648686.1 link	n.162T>A		non_coding_transcript_exon_variant	Exon 1 of 7			ENSP00000498140.1	A0A3B3IU88
TXNDC12	ENST00000371626.9 link	c.159-4559T>A		intron_variant	Intron 2 of 6	1	NM_015913.4	ENSP00000360688.4	O95881

Frequencies

GnomAD3 genomes

AF:

0.0544

AC:

8280

AN:

152186

Hom.:

279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0735

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0605

Gnomad ASJ

AF:

0.0283

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.0350

Gnomad FIN

AF:

0.0191

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0438

Gnomad OTH

AF:

0.0578

GnomAD2 exomes

AF:

0.0593

AC:

14895

AN:

251260

AF XY:

0.0556

show subpopulations

Gnomad AFR exome

AF:

0.0764

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.0280

Gnomad EAS exome

AF:

0.142

Gnomad FIN exome

AF:

0.0229

Gnomad NFE exome

AF:

0.0450

Gnomad OTH exome

AF:

0.0510

GnomAD4 exome

AF:

0.0486

AC:

71070

AN:

1461846

Hom.:

2023

Cov.:

AF XY:

0.0477

AC XY:

34672

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.0739

AC:

2473

AN:

33480

American (AMR)

AF:

0.100

AC:

4478

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0293

AC:

765

AN:

26136

East Asian (EAS)

AF:

0.112

AC:

4445

AN:

39700

South Asian (SAS)

AF:

0.0351

AC:

3028

AN:

86254

European-Finnish (FIN)

AF:

0.0215

AC:

1147

AN:

53390

Middle Eastern (MID)

AF:

0.0345

AC:

199

AN:

5768

European-Non Finnish (NFE)

AF:

0.0461

AC:

51317

AN:

1112004

Other (OTH)

AF:

0.0533

AC:

3218

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

5131

10261

15392

20522

25653

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2054

4108

6162

8216

10270

<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:

0.0546

AC:

8317

AN:

152304

Hom.:

285

Cov.:

AF XY:

0.0525

AC XY:

3910

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0740

AC:

3076

AN:

41572

American (AMR)

AF:

0.0610

AC:

933

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0283

AC:

AN:

3468

East Asian (EAS)

AF:

0.130

AC:

672

AN:

5176

South Asian (SAS)

AF:

0.0352

AC:

170

AN:

4826

European-Finnish (FIN)

AF:

0.0191

AC:

203

AN:

10626

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0438

AC:

2977

AN:

68012

Other (OTH)

AF:

0.0596

AC:

126

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

393

787

1180

1574

1967

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0497

Hom.:

174

Bravo

AF:

0.0617

TwinsUK

AF:

0.0480

AC:

178

ALSPAC

AF:

0.0514

AC:

198

ESP6500AA

AF:

0.0724

AC:

319

ESP6500EA

AF:

0.0463

AC:

398

ExAC

AF:

0.0595

AC:

7223

Asia WGS

AF:

0.0910

AC:

315

AN:

3478

EpiCase

AF:

0.0441

EpiControl

AF:

0.0466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.0060

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.0011

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.16

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.77

PhyloP100

-3.4

PrimateAI

Benign

0.34

PROVEAN

Benign

0.43

REVEL

Benign

0.046

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.012

MutPred

0.098

Loss of helix (P = 0.079);

MPC

0.52

ClinPred

0.0018

GERP RS

-5.7

Varity_R

0.040

gMVP

0.085

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over