4-6858451-G-A

Position:

• chr4-6858451-G-A

Variant summary

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

The NM_014743.3(KIAA0232):​c.463G>A​(p.Gly155Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,453,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: KIAA0232 NM_014743.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.50

Genes affected

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

KIAA0232 (HGNC:):

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=0.17974001).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0232	NM_014743.3	c.463G>A	p.Gly155Arg	missense_variant	6/10	ENST00000307659.6	NP_055558.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0232	ENST00000307659.6	c.463G>A	p.Gly155Arg	missense_variant	6/10	1	NM_014743.3	ENSP00000303928.5
KIAA0232	ENST00000425103.5	c.463G>A	p.Gly155Arg	missense_variant	5/9	1		ENSP00000413739.1
KIAA0232	ENST00000503069.1	n.194G>A		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1453584 Hom.: 0 Cov.: 28 AF XY: 0.00000415 AC XY: 3 AN XY: 723022

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000508

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000548

EpiControl AF: 0.00

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

Oct 12, 2022

The c.463G>A (p.G155R) alteration is located in exon 6 (coding exon 4) of the KIAA0232 gene. This alteration results from a G to A substitution at nucleotide position 463, causing the glycine (G) at amino acid position 155 to be replaced by an arginine (R). 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	0.29
BayesDel_addAF	Benign	-0.00083	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	T;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;.
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.10
Sift	Uncertain	0.028	D;D
Sift4G	Benign	0.28	T;T
Polyphen		0.93	P;P
Vest4		0.27
MutPred		0.25		Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);
MVP		0.082
MPC		0.59
ClinPred		0.89	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1476863445; hg19: chr4-6860178;