1-52033659-C-T

Position:

• chr1-52033659-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138417.3(KTI12):​c.103G>A​(p.Val35Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KTI12 NM_138417.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00

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]

ENSG00000223390 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KTI12	NM_138417.3	c.103G>A	p.Val35Met	missense_variant	1/1	ENST00000371614.2	NP_612426.1
TXNDC12	NM_015913.4	c.159-5029G>A		intron_variant		ENST00000371626.9	NP_056997.1
TXNDC12	NR_046405.1	n.1626G>A		non_coding_transcript_exon_variant	3/3
TXNDC12	NR_046406.1	n.1503G>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KTI12	ENST00000371614.2	c.103G>A	p.Val35Met	missense_variant	1/1	6	NM_138417.3	ENSP00000360676.1
TXNDC12	ENST00000371626.9	c.159-5029G>A		intron_variant		1	NM_015913.4	ENSP00000360688.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2022

The c.103G>A (p.V35M) 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 103, causing the valine (V) at amino acid position 35 to be replaced by a methionine (M). 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	0.58
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.71	T
MutationAssessor	Pathogenic	3.3	M
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.28
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.57		Gain of sheet (P = 0.1208);
MVP		0.57
MPC		1.5
ClinPred		0.99	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-52499331;