Variant 22-45199917-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP5

The NM_001009880.2(KIAA0930):c.971C>T(p.Ser324Leu) 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KIAA0930
NM_001009880.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:2

Conservation

PhyloP100: 9.37

Variant links:

Genes affected

KIAA0930 (HGNC:1314): (KIAA0930)

KIAA0930 links:

KIAA0930 (HGNC:):

KIAA0930 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity K0930_HUMAN

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 22-45199917-G-A is Pathogenic according to our data. Variant chr22-45199917-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1691076.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=2, Likely_pathogenic=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0930	NM_001009880.2 linkuse as main transcript	c.971C>T	p.Ser324Leu	missense_variant	8/10	ENST00000336156.10	NP_001009880.1	Q6ICG6-1
KIAA0930	NM_015264.2 linkuse as main transcript	c.986C>T	p.Ser329Leu	missense_variant	8/10		NP_056079.1	Q6ICG6-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0930	ENST00000336156.10 linkuse as main transcript	c.971C>T	p.Ser324Leu	missense_variant	8/10	1	NM_001009880.2	ENSP00000336720.4		Q6ICG6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1452916

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721876

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Neurodevelopmental disorder

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Hadassah Hebrew University Medical Center

Apr 01, 2023

- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2023

The c.986C>T (p.S329L) alteration is located in exon 8 (coding exon 8) of the KIAA0930 gene. This alteration results from a C to T substitution at nucleotide position 986, causing the serine (S) at amino acid position 329 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, flagged submission

clinical testing

Hadassah Hebrew University Medical Center

Apr 17, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.059

T;T;.;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D;D;D

M_CAP

Benign

0.075

MetaRNN

Uncertain

0.54

D;D;D;D

MetaSVM

Uncertain

-0.22

MutationAssessor

Benign

0.97

L;.;.;.

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-2.3

N;N;N;N

REVEL

Benign

0.28

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Benign

0.17

T;T;T;T

Polyphen

0.96

D;.;D;.

Vest4

0.74

MutPred

0.14

Loss of phosphorylation at S324 (P = 0.0136);.;.;.;

MVP

0.18

MPC

1.3

ClinPred

0.91

GERP RS

4.9

Varity_R

0.33

gMVP

0.81

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over