22-45203004-G-A

Position:

• chr22-45203004-G-A

Variant summary

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

The NM_001009880.2(KIAA0930):​c.838C>T​(p.Pro280Ser) variant causes a missense change involving the alteration of a conserved nucleotide. 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: KIAA0930 NM_001009880.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.44

Genes affected

KIAA0930 (HGNC:1314): (KIAA0930)

KIAA0930 (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
KIAA0930	NM_001009880.2	c.838C>T	p.Pro280Ser	missense_variant	7/10	ENST00000336156.10	NP_001009880.1
KIAA0930	NM_015264.2	c.853C>T	p.Pro285Ser	missense_variant	7/10		NP_056079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0930	ENST00000336156.10	c.838C>T	p.Pro280Ser	missense_variant	7/10	1	NM_001009880.2	ENSP00000336720.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

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 09, 2024

The c.853C>T (p.P285S) alteration is located in exon 7 (coding exon 7) of the KIAA0930 gene. This alteration results from a C to T substitution at nucleotide position 853, causing the proline (P) at amino acid position 285 to be replaced by a serine (S). 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	0.11
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T;T;.;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.46	T;T;T;T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	0.90	L;.;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Benign	0.22
Sift	Uncertain	0.0080	D;D;T;D
Sift4G	Benign	0.20	T;T;T;T
Polyphen		0.95	P;.;B;.
Vest4		0.68
MutPred		0.17		Gain of phosphorylation at P280 (P = 0.0142);.;.;.;
MVP		0.12
MPC		1.3
ClinPred		0.93	D
GERP RS		4.9
Varity_R		0.21
gMVP		0.64

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

LitVar

Other links and lift over

dbSNP: rs1831567641; hg19: chr22-45598885;