1-52032782-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_138417.3(KTI12):c.980C>G(p.Ser327Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

KTI12
NM_138417.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.85

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.799

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KTI12	NM_138417.3 link	c.980C>G	p.Ser327Trp	missense_variant	Exon 1 of 1	ENST00000371614.2	NP_612426.1	Q96EK9
TXNDC12	NM_015913.4 link	c.159-4152C>G		intron_variant	Intron 2 of 6	ENST00000371626.9	NP_056997.1	O95881
TXNDC12	NR_046405.1 link	n.2503C>G		non_coding_transcript_exon_variant	Exon 3 of 3
TXNDC12	NR_046406.1 link	n.2380C>G		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.980C>G	p.Ser327Trp	missense_variant	Exon 1 of 1	6	NM_138417.3	ENSP00000360676.1	Q96EK9
TXNDC12	ENST00000371626.9 link	c.159-4152C>G		intron_variant	Intron 2 of 6	1	NM_015913.4	ENSP00000360688.4	O95881
ENSG00000285839	ENST00000648686.1 link	n.569C>G		non_coding_transcript_exon_variant	Exon 1 of 7			ENSP00000498140.1	A0A3B3IU88
TXNDC12	ENST00000472624.5 link	n.159-2234C>G		intron_variant	Intron 2 of 7	5		ENSP00000477120.1	V9GYV4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251460

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135898

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:

0.0000924

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727244

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:

0.0000374

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.980C>G (p.S327W) alteration is located in exon 1 (coding exon 1) of the KTI12 gene. This alteration results from a C to G substitution at nucleotide position 980, causing the serine (S) at amino acid position 327 to be replaced by a tryptophan (W). 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

Pathogenic

0.86

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.044

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Benign

0.38

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.090

MetaRNN

Pathogenic

0.80

MetaSVM

Benign

-0.66

MutationAssessor

Pathogenic

3.0

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-4.7

REVEL

Uncertain

0.46

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.69

MVP

0.69

MPC

1.8

ClinPred

0.97

GERP RS

4.6

Varity_R

0.57

gMVP

0.56

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over