1-52032956-C-T

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

19

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]
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]

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
KTI12NM_138417.3 linkc.806G>A p.Ser269Asn missense_variant Exon 1 of 1 ENST00000371614.2 NP_612426.1 Q96EK9
TXNDC12NM_015913.4 linkc.159-4326G>A intron_variant Intron 2 of 6 ENST00000371626.9 NP_056997.1 O95881
TXNDC12NR_046405.1 linkn.2329G>A non_coding_transcript_exon_variant Exon 3 of 3
TXNDC12NR_046406.1 linkn.2206G>A non_coding_transcript_exon_variant Exon 3 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KTI12ENST00000371614.2 linkc.806G>A p.Ser269Asn missense_variant Exon 1 of 1 6 NM_138417.3 ENSP00000360676.1 Q96EK9
TXNDC12ENST00000371626.9 linkc.159-4326G>A intron_variant Intron 2 of 6 1 NM_015913.4 ENSP00000360688.4 O95881
ENSG00000285839ENST00000648686.1 linkn.395G>A non_coding_transcript_exon_variant Exon 1 of 7 ENSP00000498140.1 A0A3B3IU88
TXNDC12ENST00000472624.5 linkn.159-2408G>A intron_variant Intron 2 of 7 5 ENSP00000477120.1 V9GYV4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000221
AC:
5
AN:
225812
Hom.:
0
AF XY:
0.0000247
AC XY:
3
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:
16
AN:
1436064
Hom.:
0
Cov.:
33
AF XY:
0.0000154
AC XY:
11
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.:
33
Bravo
AF:
0.00000756
ExAC
AF:
0.0000330
AC:
4

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
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
1.1
DANN
Benign
0.94
DEOGEN2
Benign
0.0019
T
Eigen
Benign
-0.96
Eigen_PC
Benign
-0.79
FATHMM_MKL
Benign
0.041
N
LIST_S2
Benign
0.67
T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.036
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
-0.44
N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
3.2
N
REVEL
Benign
0.063
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0010
B
Vest4
0.047
MutPred
0.46
Loss of disorder (P = 0.0798);
MVP
0.15
MPC
0.52
ClinPred
0.051
T
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.

Other links and lift over

dbSNP: rs762348795; hg19: chr1-52498628; API