Genetic Variant KIAA0825:p.Thr736del (chr5-94462424-ATGT-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PM4_SupportingBP6

The NM_001145678.3(KIAA0825):c.2206_2208delACA(p.Thr736del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.000229 in 1,472,994 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

KIAA0825
NM_001145678.3 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.68

Variant links:

Genes affected

KIAA0825 (HGNC:28532): (KIAA0825)

KIAA0825 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_001145678.3. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 5-94462424-ATGT-A is Benign according to our data. Variant chr5-94462424-ATGT-A is described in ClinVar as [Likely_benign]. Clinvar id is 3045394.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0825	NM_001145678.3 link	c.2206_2208delACA	p.Thr736del	conservative_inframe_deletion	Exon 12 of 21	ENST00000682413.1	NP_001139150.1	A0A804HHT9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KIAA0825	ENST00000682413.1 link	c.2206_2208delACA	p.Thr736del	conservative_inframe_deletion	Exon 12 of 21		NM_001145678.3	ENSP00000506760.1	A0A804HHT9
KIAA0825	ENST00000504117.1 link	n.1053_1055delACA		non_coding_transcript_exon_variant	Exon 6 of 9	1
KIAA0825	ENST00000703867.1 link	c.2206_2208delACA	p.Thr736del	conservative_inframe_deletion	Exon 12 of 21			ENSP00000515512.1	A0A994J718
KIAA0825	ENST00000513200.7 link	c.2206_2208delACA	p.Thr736del	conservative_inframe_deletion	Exon 11 of 20	5		ENSP00000424618.2	Q8IV33-1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

151930

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00318

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000396

AC:

AN:

141388

Hom.:

AF XY:

0.000334

AC XY:

AN XY:

74818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000482

Gnomad ASJ exome

AF:

0.00517

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000250

Gnomad OTH exome

AF:

0.000253

GnomAD4 exome

AF:

0.000236

AC:

312

AN:

1321064

Hom.:

AF XY:

0.000214

AC XY:

140

AN XY:

654104

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000619

Gnomad4 ASJ exome

AF:

0.00398

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000189

Gnomad4 OTH exome

AF:

0.000398

GnomAD4 genome

AF:

0.000171

AC:

AN:

151930

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00318

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000912

Hom.:

Bravo

AF:

0.000219

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KIAA0825-related disorder

Benign:1

Jun 04, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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