Variant chr9-112659570-G-A 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.1652G>A(p.Ser551Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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: 0.0000021 ( 0 hom. )

Consequence

KIAA1958
ENST00000337530.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.21

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=0.17111811).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1958	NM_133465.4 linkuse as main transcript	c.1652G>A	p.Ser551Asn	missense_variant	4/4	ENST00000337530.11	NP_597722.1	Q8N8K9-1
KIAA1958	NM_001287036.2 linkuse as main transcript	c.1736G>A	p.Ser579Asn	missense_variant	5/5		NP_001273965.1	Q8N8K9-3
KIAA1958	NM_001287038.2 linkuse as main transcript	c.*295G>A		3_prime_UTR_variant	4/4		NP_001273967.1	Q8N8K9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA1958	ENST00000337530.11 linkuse as main transcript	c.1652G>A	p.Ser551Asn	missense_variant	4/4	1	NM_133465.4	ENSP00000336940.6		Q8N8K9-1
KIAA1958	ENST00000536272.5 linkuse as main transcript	c.1736G>A	p.Ser579Asn	missense_variant	5/5	1		ENSP00000440504.1		Q8N8K9-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248330

Hom.:

AF XY:

0.00000745

AC XY:

AN XY:

134284

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000874

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:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460804

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726644

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000673

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.:

Bravo

AF:

0.00000756

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

Oct 26, 2021

The c.1652G>A (p.S551N) alteration is located in exon 4 (coding exon 3) of the KIAA1958 gene. This alteration results from a G to A substitution at nucleotide position 1652, causing the serine (S) at amino acid position 551 to be replaced by an asparagine (N). 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

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.31

DEOGEN2

Benign

0.045

T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

0.086

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.46

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.48

N;N

REVEL

Benign

0.23

Sift

Benign

0.89

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;.

Vest4

0.20

MutPred

0.39

Loss of catalytic residue at S551 (P = 0.1031);.;

MVP

0.54

MPC

0.25

ClinPred

0.045

GERP RS

5.7

Varity_R

0.051

gMVP

0.34

Splicing

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