4-6824611-A-T

Position:

• chr4-6824611-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014743.3(KIAA0232):​c.158A>T​(p.Asp53Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 8.93

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.825

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0232	NM_014743.3	c.158A>T	p.Asp53Val	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.158A>T	p.Asp53Val	missense_variant	3/10	1	NM_014743.3	ENSP00000303928.5
KIAA0232	ENST00000425103.5	c.158A>T	p.Asp53Val	missense_variant	2/9	1		ENSP00000413739.1
KIAA0232	ENST00000508423.1	c.158A>T	p.Asp53Val	missense_variant	2/2	2		ENSP00000426815.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

KIAA0232-related disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 06, 2023

The KIAA0232 c.158A>T variant is predicted to result in the amino acid substitution p.Asp53Val. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	.;T;T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D;D;.
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	2.0	.;M;M
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-9.0	D;D;D
REVEL	Uncertain	0.55
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.99
MutPred		0.60		Gain of sheet (P = 0.0043);Gain of sheet (P = 0.0043);Gain of sheet (P = 0.0043);
MVP		0.59
MPC		0.87
ClinPred		1.0	D
GERP RS		6.1
Varity_R		0.91
gMVP		0.75

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: chr4-6826338;