Variant 1-32769770-T-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 NM_020888.3(KIAA1522):c.684T>A(p.His228Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000314 in 1,613,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

KIAA1522
NM_020888.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.68

Variant links:

Genes affected

KIAA1522 (HGNC:29301): (NHS like 3) Predicted to be involved in cell differentiation. [provided by Alliance of Genome Resources, Apr 2022]

KIAA1522 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=0.19376105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KIAA1522	NM_020888.3 linkuse as main transcript	c.684T>A	p.His228Gln	missense_variant	5/7	ENST00000401073.7	NP_065939.2
KIAA1522	NM_001369553.1 linkuse as main transcript	c.540T>A	p.His180Gln	missense_variant	5/7		NP_001356482.1
KIAA1522	NM_001198972.2 linkuse as main transcript	c.507T>A	p.His169Gln	missense_variant	5/7		NP_001185901.1
KIAA1522	NM_001198973.2 linkuse as main transcript	c.409+995T>A		intron_variant			NP_001185902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA1522	ENST00000401073.7 linkuse as main transcript	c.684T>A	p.His228Gln	missense_variant	5/7	2	NM_020888.3	ENSP00000383851	A2	Q9P206-2
KIAA1522	ENST00000373480.1 linkuse as main transcript	c.507T>A	p.His169Gln	missense_variant	5/7	1		ENSP00000362579	P2	Q9P206-1
KIAA1522	ENST00000373481.7 linkuse as main transcript	c.540T>A	p.His180Gln	missense_variant	5/7	2		ENSP00000362580	A2	Q9P206-3
KIAA1522	ENST00000294521.7 linkuse as main transcript	c.409+995T>A		intron_variant		2		ENSP00000294521	A2	Q9P206-4

Frequencies

GnomAD3 genomes

AF:

0.000277

AC:

AN:

151888

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000486

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000571

AC:

142

AN:

248522

Hom.:

AF XY:

0.000600

AC XY:

AN XY:

134952

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000234

Gnomad NFE exome

AF:

0.00115

Gnomad OTH exome

AF:

0.000498

GnomAD4 exome

AF:

0.000317

AC:

464

AN:

1461632

Hom.:

Cov.:

AF XY:

0.000311

AC XY:

226

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000244

Gnomad4 NFE exome

AF:

0.000387

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000277

AC:

AN:

151888

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000190

Gnomad4 NFE

AF:

0.000486

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000401

Hom.:

Bravo

AF:

0.000242

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000252

AC:

ESP6500EA

AF:

0.000361

AC:

ExAC

AF:

0.000951

AC:

115

EpiCase

AF:

0.000327

EpiControl

AF:

0.000237

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

May 29, 2024

The c.684T>A (p.H228Q) alteration is located in exon 5 (coding exon 5) of the KIAA1522 gene. This alteration results from a T to A substitution at nucleotide position 684, causing the histidine (H) at amino acid position 228 to be replaced by a glutamine (Q). 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

Pathogenic

0.85

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.38

CADD

Benign

0.020

DANN

Benign

0.72

DEOGEN2

Benign

0.017

.;.;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

.;.;L

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.4

N;N;N

REVEL

Benign

0.22

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.54

T;T;T

Polyphen

0.98

D;D;D

Vest4

0.69

MutPred

0.12

.;.;Gain of MoRF binding (P = 0.0917);

MVP

0.38

MPC

0.12

ClinPred

0.13

GERP RS

-5.5

Varity_R

0.078

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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