1-52033265-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_138417.3(KTI12):c.497C>T(p.Ala166Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KTI12
NM_138417.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0990

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043498755).

BP6

Variant 1-52033265-G-A is Benign according to our data. Variant chr1-52033265-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2283572.Status of the report is criteria_provided_single_submitter, 1 stars.

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.497C>T	p.Ala166Val	missense	Exon 1 of 1	NP_612426.1	Q96EK9
TXNDC12	NM_015913.4	MANE Select	c.159-4635C>T		intron	N/A	NP_056997.1	O95881
TXNDC12	NR_046405.1		n.2020C>T		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.497C>T	p.Ala166Val	missense	Exon 1 of 1	ENSP00000360676.1	Q96EK9
TXNDC12	ENST00000371626.9	TSL:1 MANE Select	c.159-4635C>T		intron	N/A	ENSP00000360688.4	O95881
ENSG00000285839	ENST00000648686.1		n.86C>T		non_coding_transcript_exon	Exon 1 of 7	ENSP00000498140.1	A0A3B3IU88

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461646

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727110

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111934

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.1

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0023

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.33

M_CAP

Benign

0.0036

MetaRNN

Benign

0.043

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PhyloP100

-0.099

PrimateAI

Benign

0.35

PROVEAN

Benign

0.040

REVEL

Benign

0.022

Sift

Benign

1.0

Sift4G

Benign

0.52

Polyphen

0.0010

Vest4

0.029

MutPred

0.34

Gain of helix (P = 0.062)

MVP

0.22

MPC

0.55

ClinPred

0.052

GERP RS

0.99

Varity_R

0.020

gMVP

0.19

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over