Variant 9-112574810-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000337530.11(KIAA1958):c.730C>T(p.Pro244Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

KIAA1958
ENST00000337530.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.68

Variant links:

Genes affected

KIAA1958 (HGNC:23427): (KIAA1958)

KIAA1958 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12777871).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1958	NM_133465.4 linkuse as main transcript	c.730C>T	p.Pro244Ser	missense_variant	2/4	ENST00000337530.11	NP_597722.1	Q8N8K9-1
KIAA1958	NM_001287036.2 linkuse as main transcript	c.730C>T	p.Pro244Ser	missense_variant	2/5		NP_001273965.1	Q8N8K9-3
KIAA1958	NM_001287038.2 linkuse as main transcript	c.730C>T	p.Pro244Ser	missense_variant	2/4		NP_001273967.1	Q8N8K9
KIAA1958	XM_011518311.3 linkuse as main transcript	c.730C>T	p.Pro244Ser	missense_variant	2/3		XP_011516613.1	Q8N8K9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KIAA1958	ENST00000337530.11 linkuse as main transcript	c.730C>T	p.Pro244Ser	missense_variant	2/4	1	NM_133465.4	ENSP00000336940.6	Q8N8K9-1
KIAA1958	ENST00000536272.5 linkuse as main transcript	c.730C>T	p.Pro244Ser	missense_variant	2/5	1		ENSP00000440504.1	Q8N8K9-3
KIAA1958	ENST00000374244.3 linkuse as main transcript	c.730C>T	p.Pro244Ser	missense_variant	2/3	5		ENSP00000363362.3	Q8N8K9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251054

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135664

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

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:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2022

The c.730C>T (p.P244S) alteration is located in exon 2 (coding exon 1) of the KIAA1958 gene. This alteration results from a C to T substitution at nucleotide position 730, causing the proline (P) at amino acid position 244 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

0.085

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.052

T;.;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N

MutationTaster

Benign

0.81

D;D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.071

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.48

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.26

MutPred

0.29

Gain of phosphorylation at P244 (P = 0.0707);Gain of phosphorylation at P244 (P = 0.0707);Gain of phosphorylation at P244 (P = 0.0707);

MVP

0.64

MPC

0.27

ClinPred

0.048

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.048

gMVP

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over