Variant 5-94391521-GGCCGTTTCCCTACCTCATT-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_001145678.3(KIAA0825):c.3451_3456+13del variant causes a splice donor, splice donor 5th base, coding sequence, intron change. The variant allele was found at a frequency of 0.000573 in 1,551,326 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 1 hom. )

Consequence

KIAA0825
NM_001145678.3 splice_donor, splice_donor_5th_base, coding_sequence, intron

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 5.72

Variant links:

Genes affected

KIAA0825 (HGNC:28532): (KIAA0825)

KIAA0825 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, Cryptic splice site detected, with MaxEntScore 4.3, offset of 32, new splice context is: tagGTgtgt. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 5-94391521-GGCCGTTTCCCTACCTCATT-G is Pathogenic according to our data. Variant chr5-94391521-GGCCGTTTCCCTACCTCATT-G is described in ClinVar as [Pathogenic]. Clinvar id is 2500276.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0825	NM_001145678.3 linkuse as main transcript	c.3451_3456+13del		splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	18/21	ENST00000682413.1	NP_001139150.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0825	ENST00000682413.1 linkuse as main transcript	c.3451_3456+13del	splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	18/21		NM_001145678.3	ENSP00000506760	A1
KIAA0825	ENST00000513200.7 linkuse as main transcript	c.3451_3456+13del	splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	17/20	5		ENSP00000424618	A1	Q8IV33-1
KIAA0825	ENST00000703867.1 linkuse as main transcript	c.3466_3471+13del	splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	18/21			ENSP00000515512	P4

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000301

AC:

AN:

156252

Hom.:

AF XY:

0.000362

AC XY:

AN XY:

82784

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000405

Gnomad ASJ exome

AF:

0.000354

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000595

Gnomad NFE exome

AF:

0.000664

Gnomad OTH exome

AF:

0.000456

GnomAD4 exome

AF:

0.000589

AC:

824

AN:

1399116

Hom.:

AF XY:

0.000577

AC XY:

398

AN XY:

690070

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

Gnomad4 AMR exome

AF:

0.0000840

Gnomad4 ASJ exome

AF:

0.000318

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000609

Gnomad4 NFE exome

AF:

0.000717

Gnomad4 OTH exome

AF:

0.000552

GnomAD4 genome

AF:

0.000427

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000738

Hom.:

Bravo

AF:

0.000468

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Polydactyly, postaxial, type a10

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Equipe Genetique des Anomalies du Developpement, Université de Bourgogne

Apr 11, 2023

This variant was observed in heterozygosity with variant c.2020T>A -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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