Genetic Variant KIAA0930:p.Ala325Thr (chr22-45199915-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4

The NM_001009880.2(KIAA0930):c.973G>A(p.Ala325Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 7.39

Publications

0 publications found

Variant links:

Genes affected

KIAA0930 (HGNC:1314): (KIAA0930)

KIAA0930 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 22-45199915-C-T is Pathogenic according to our data. Variant chr22-45199915-C-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 1691077.Status of the report is criteria_provided_single_submitter, 1 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.4123056). . Strength limited to SUPPORTING due to the PP5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009880.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0930	NM_001009880.2	MANE Select	c.973G>A	p.Ala325Thr	missense	Exon 8 of 10	NP_001009880.1	Q6ICG6-1
	KIAA0930	NM_015264.2		c.988G>A	p.Ala330Thr	missense	Exon 8 of 10	NP_056079.1	Q6ICG6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIAA0930	ENST00000336156.10	TSL:1 MANE Select	c.973G>A	p.Ala325Thr	missense	Exon 8 of 10	ENSP00000336720.4	Q6ICG6-1
KIAA0930	ENST00000391627.6	TSL:1	c.871G>A	p.Ala291Thr	missense	Exon 8 of 10	ENSP00000375485.2	Q6ICG6-3
KIAA0930	ENST00000488038.5	TSL:1	n.1259G>A		non_coding_transcript_exon	Exon 7 of 9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1452046

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721314

African (AFR)

AF:

0.00

AC:

AN:

33022

American (AMR)

AF:

0.00

AC:

AN:

43892

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25922

East Asian (EAS)

AF:

0.00

AC:

AN:

38900

South Asian (SAS)

AF:

0.00

AC:

AN:

85346

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53336

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105944

Other (OTH)

AF:

0.00

AC:

AN:

59938

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Neurodevelopmental disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.031

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.49

MutationAssessor

Benign

0.90

PhyloP100

7.4

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.80

REVEL

Benign

0.19

Sift

Benign

0.37

Sift4G

Benign

0.42

Polyphen

1.0

Vest4

0.78

MutPred

0.12

Gain of glycosylation at A325 (P = 0.0209)

MVP

0.10

MPC

1.1

ClinPred

0.93

GERP RS

4.9

Varity_R

0.10

gMVP

0.66

Mutation Taster

=28/72

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over