1-52032956-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138417.3(KTI12):c.806G>A(p.Ser269Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 1,436,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

KTI12
NM_138417.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.78

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.036443353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KTI12	NM_138417.3 link	c.806G>A	p.Ser269Asn	missense_variant	Exon 1 of 1	ENST00000371614.2	NP_612426.1	Q96EK9
TXNDC12	NM_015913.4 link	c.159-4326G>A		intron_variant	Intron 2 of 6	ENST00000371626.9	NP_056997.1	O95881
TXNDC12	NR_046405.1 link	n.2329G>A		non_coding_transcript_exon_variant	Exon 3 of 3
TXNDC12	NR_046406.1 link	n.2206G>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.806G>A	p.Ser269Asn	missense_variant	Exon 1 of 1	6	NM_138417.3	ENSP00000360676.1	Q96EK9
TXNDC12	ENST00000371626.9 link	c.159-4326G>A		intron_variant	Intron 2 of 6	1	NM_015913.4	ENSP00000360688.4	O95881
ENSG00000285839	ENST00000648686.1 link	n.395G>A		non_coding_transcript_exon_variant	Exon 1 of 7			ENSP00000498140.1	A0A3B3IU88
TXNDC12	ENST00000472624.5 link	n.159-2408G>A		intron_variant	Intron 2 of 7	5		ENSP00000477120.1	V9GYV4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000221

AC:

AN:

225812

Hom.:

AF XY:

0.0000247

AC XY:

AN XY:

121612

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000484

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000111

AC:

AN:

1436064

Hom.:

Cov.:

AF XY:

0.0000154

AC XY:

AN XY:

712566

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000145

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.806G>A (p.S269N) alteration is located in exon 1 (coding exon 1) of the KTI12 gene. This alteration results from a G to A substitution at nucleotide position 806, causing the serine (S) at amino acid position 269 to be replaced by an asparagine (N). 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

0.10

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.1

DANN

Benign

0.94

DEOGEN2

Benign

0.0019

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.67

M_CAP

Benign

0.013

MetaRNN

Benign

0.036

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.44

PrimateAI

Benign

0.36

PROVEAN

Benign

3.2

REVEL

Benign

0.063

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.047

MutPred

0.46

Loss of disorder (P = 0.0798);

MVP

0.15

MPC

0.52

ClinPred

0.051

GERP RS

1.7

Varity_R

0.045

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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