chr22-45199923-G-A

Position:

• chr22-45199923-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_001009880.2(KIAA0930):​c.965C>T​(p.Ser322Leu) 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 Likely pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIAA0930 NM_001009880.2 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1 U:1
• Conservation: PhyloP100: 9.37

Genes affected

KIAA0930 (HGNC:1314): (KIAA0930)

KIAA0930 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 22-45199923-G-A is Pathogenic according to our data. Variant chr22-45199923-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1691075.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0930	NM_001009880.2	c.965C>T	p.Ser322Leu	missense_variant	8/10	ENST00000336156.10	NP_001009880.1
KIAA0930	NM_015264.2	c.980C>T	p.Ser327Leu	missense_variant	8/10		NP_056079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0930	ENST00000336156.10	c.965C>T	p.Ser322Leu	missense_variant	8/10	1	NM_001009880.2	ENSP00000336720.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1454116 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 722620

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.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1 Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodevelopmental disorder Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Hadassah Hebrew University Medical Center

Apr 01, 2023

- -

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	0.89
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.071	T;T;.;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.44	T;T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.90	L;.;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-2.0	N;N;N;N
REVEL	Benign	0.27
Sift	Benign	0.20	T;T;T;T
Sift4G	Benign	0.13	T;T;T;T
Polyphen		1.0	D;.;D;.
Vest4		0.81
MutPred		0.15		Loss of phosphorylation at S322 (P = 0.0103);.;.;.;
MVP		0.25
MPC		1.0
ClinPred		0.93	D
GERP RS		4.9
Varity_R		0.11
gMVP		0.61

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: chr22-45595804; COSMIC: COSV52666005; COSMIC: COSV52666005;