chr1-52033189-A-T

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:

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:

ENSG00000285839 (HGNC:):

ENSG00000285839 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138417.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KTI12	NM_138417.3	MANE Select	c.573T>A	p.Asp191Glu	missense	Exon 1 of 1	NP_612426.1	Q96EK9
TXNDC12	NM_015913.4	MANE Select	c.159-4559T>A		intron	N/A	NP_056997.1	O95881
TXNDC12	NR_046405.1		n.2096T>A		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KTI12	ENST00000371614.2	TSL:6 MANE Select	c.573T>A	p.Asp191Glu	missense	Exon 1 of 1	ENSP00000360676.1	Q96EK9
TXNDC12	ENST00000371626.9	TSL:1 MANE Select	c.159-4559T>A		intron	N/A	ENSP00000360688.4	O95881
ENSG00000285839	ENST00000648686.1		n.162T>A		non_coding_transcript_exon	Exon 1 of 7	ENSP00000498140.1	A0A3B3IU88

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over