4-6824457-T-C

Position:

• chr4-6824457-T-C

Variant summary

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

The NM_014743.3(KIAA0232):​c.4T>C​(p.Tyr2His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 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: 3.60

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=0.08477062).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0232	NM_014743.3	c.4T>C	p.Tyr2His	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.4T>C	p.Tyr2His	missense_variant	3/10	1	NM_014743.3	ENSP00000303928.5
KIAA0232	ENST00000425103.5	c.4T>C	p.Tyr2His	missense_variant	2/9	1		ENSP00000413739.1
KIAA0232	ENST00000508423.1	c.4T>C	p.Tyr2His	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

Mar 30, 2024

The c.4T>C (p.Y2H) alteration is located in exon 3 (coding exon 1) of the KIAA0232 gene. This alteration results from a T to C substitution at nucleotide position 4, causing the tyrosine (Y) at amino acid position 2 to be replaced by a histidine (H). 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	0.058
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.023	.;T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.44	T;T;.
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.085	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	1.2	N;N;N
REVEL	Benign	0.030
Sift	Benign	0.14	T;T;T
Sift4G	Benign	0.16	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.072
MutPred		0.38		Gain of disorder (P = 0.0329);Gain of disorder (P = 0.0329);Gain of disorder (P = 0.0329);
MVP		0.043
MPC		0.23
ClinPred		0.15	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.030
gMVP		0.28

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: chr4-6826184;