4-6824470-C-T

Position:

• chr4-6824470-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014743.3(KIAA0232):​c.17C>T​(p.Thr6Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIAA0232 NM_014743.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.40

Genes affected

KIAA0232 (HGNC:28992): (KIAA0232) Predicted to enable ATP binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21039778).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0232	NM_014743.3	c.17C>T	p.Thr6Ile	missense_variant	3/10	ENST00000307659.6	NP_055558.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0232	ENST00000307659.6	c.17C>T	p.Thr6Ile	missense_variant	3/10	1	NM_014743.3	ENSP00000303928.5
KIAA0232	ENST00000425103.5	c.17C>T	p.Thr6Ile	missense_variant	2/9	1		ENSP00000413739.1
KIAA0232	ENST00000508423.1	c.17C>T	p.Thr6Ile	missense_variant	2/2	2		ENSP00000426815.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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 23, 2024

The c.17C>T (p.T6I) alteration is located in exon 3 (coding exon 1) of the KIAA0232 gene. This alteration results from a C to T substitution at nucleotide position 17, causing the threonine (T) at amino acid position 6 to be replaced by an isoleucine (I). 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	0.20
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.081	.;T;T
Eigen	Benign	-0.063
Eigen_PC	Benign	0.019
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.80	T;T;.
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.4	.;L;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.4	D;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.016	D;D;D
Polyphen		0.57	.;P;P
Vest4		0.40
MutPred		0.31		Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);
MVP		0.043
MPC		0.36
ClinPred		0.86	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.15
gMVP		0.48

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: chr4-6826197;