1-52033146-G-T

Position:

chr1-52033146-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_138417.3(KTI12):c.616C>A(p.Pro206Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,614,212 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.00021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 3 hom. )

Consequence

KTI12
NM_138417.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.41

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018506259).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KTI12	NM_138417.3 linkuse as main transcript	c.616C>A	p.Pro206Thr	missense_variant	1/1	ENST00000371614.2	NP_612426.1	Q96EK9
TXNDC12	NM_015913.4 linkuse as main transcript	c.159-4516C>A		intron_variant		ENST00000371626.9	NP_056997.1	O95881
TXNDC12	NR_046405.1 linkuse as main transcript	n.2139C>A		non_coding_transcript_exon_variant	3/3
TXNDC12	NR_046406.1 linkuse as main transcript	n.2016C>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KTI12	ENST00000371614.2 linkuse as main transcript	c.616C>A	p.Pro206Thr	missense_variant	1/1	6	NM_138417.3	ENSP00000360676.1	Q96EK9
TXNDC12	ENST00000371626.9 linkuse as main transcript	c.159-4516C>A		intron_variant		1	NM_015913.4	ENSP00000360688.4	O95881
ENSG00000285839	ENST00000648686.1 linkuse as main transcript	n.205C>A		non_coding_transcript_exon_variant	1/7			ENSP00000498140.1	A0A3B3IU88
TXNDC12	ENST00000472624.5 linkuse as main transcript	n.159-2598C>A		intron_variant		5		ENSP00000477120.1	V9GYV4

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000311

AC:

AN:

251158

Hom.:

AF XY:

0.000361

AC XY:

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.000617

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00216

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000122

AC:

179

AN:

1461846

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

116

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00173

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000210

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000721

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000394

Hom.:

Bravo

AF:

0.000208

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000371

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2024

The c.616C>A (p.P206T) alteration is located in exon 1 (coding exon 1) of the KTI12 gene. This alteration results from a C to A substitution at nucleotide position 616, causing the proline (P) at amino acid position 206 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0070

Eigen

Benign

0.034

Eigen_PC

Benign

-0.0070

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.52

M_CAP

Benign

0.020

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.4

REVEL

Benign

0.082

Sift

Benign

0.047

Sift4G

Benign

0.088

Polyphen

0.81

Vest4

0.16

MVP

0.49

MPC

1.2

ClinPred

0.10

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.054

gMVP

0.27

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over