22-45205631-T-G

Position:

• chr22-45205631-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_001009880.2(KIAA0930):​c.413A>C​(p.Gln138Pro) variant causes a missense, splice region 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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.00020 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIAA0930 NM_001009880.2 missense, splice_region
• Scores: Splicing: ADA: 0.2653
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.80

Genes affected

KIAA0930 (HGNC:1314): (KIAA0930)

KIAA0930 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.793

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0930	NM_001009880.2	c.413A>C	p.Gln138Pro	missense_variant, splice_region_variant	4/10	ENST00000336156.10	NP_001009880.1
KIAA0930	NM_015264.2	c.428A>C	p.Gln143Pro	missense_variant, splice_region_variant	4/10		NP_056079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0930	ENST00000336156.10	c.413A>C	p.Gln138Pro	missense_variant, splice_region_variant	4/10	1	NM_001009880.2	ENSP00000336720.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000202 AC: 294 AN: 1452860 Hom.: 0 Cov.: 33 AF XY: 0.000198 AC XY: 143 AN XY: 723206

Gnomad4 AFR exome AF: 0.000180

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000698

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000245

Gnomad4 OTH exome AF: 0.000116

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

May 09, 2024

The c.428A>C (p.Q143P) alteration is located in exon 4 (coding exon 4) of the KIAA0930 gene. This alteration results from a A to C substitution at nucleotide position 428, causing the glutamine (Q) at amino acid position 143 to be replaced by a proline (P). 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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.29	T;T;.;.;.;.
Eigen	Benign	0.094
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.82	T;D;T;T;T;T
M_CAP	Uncertain	0.090	D
MetaRNN	Pathogenic	0.79	D;D;D;D;D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.4	M;.;.;.;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-5.6	D;D;D;D;D;D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0020	D;D;D;D;D;D
Sift4G	Uncertain	0.012	D;D;D;D;.;D
Polyphen		0.0030	B;.;B;.;.;.
Vest4		0.94
MutPred		0.66		Loss of sheet (P = 0.0357);.;.;.;.;.;
MVP		0.27
MPC		0.59
ClinPred		0.98	D
GERP RS		3.6
Varity_R		0.67
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.27
dbscSNV1_RF	Benign	0.58
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: chr22-45601512;