1-52032948-G-A

Position:

• chr1-52032948-G-A

Variant summary

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

The ENST00000371626.9(TXNDC12):​c.159-4318C>T variant causes a intron 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: TXNDC12 ENST00000371626.9 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.08

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]

ENSG00000285839 (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.814C>T	p.His272Tyr	missense_variant	1/1	ENST00000371614.2	NP_612426.1
TXNDC12	NM_015913.4	c.159-4318C>T		intron_variant		ENST00000371626.9	NP_056997.1
TXNDC12	NR_046405.1	n.2337C>T		non_coding_transcript_exon_variant	3/3
TXNDC12	NR_046406.1	n.2214C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KTI12	ENST00000371614.2	c.814C>T	p.His272Tyr	missense_variant	1/1	6	NM_138417.3	ENSP00000360676.1
TXNDC12	ENST00000371626.9	c.159-4318C>T		intron_variant		1	NM_015913.4	ENSP00000360688.4
ENSG00000285839	ENST00000648686.1	n.403C>T		non_coding_transcript_exon_variant	1/7			ENSP00000498140.1
TXNDC12	ENST00000472624.5	n.159-2400C>T		intron_variant		5		ENSP00000477120.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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

Aug 19, 2023

The c.814C>T (p.H272Y) alteration is located in exon 1 (coding exon 1) of the KTI12 gene. This alteration results from a C to T substitution at nucleotide position 814, causing the histidine (H) at amino acid position 272 to be replaced by a tyrosine (Y). 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	0.12
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-0.062
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.15
Sift	Benign	0.47	T
Sift4G	Benign	0.61	T
Polyphen		0.28	B
Vest4		0.64
MutPred		0.46		Loss of disorder (P = 0.0331);
MVP		0.39
MPC		0.67
ClinPred		0.83	D
GERP RS		4.8
Varity_R		0.28
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-52498620;