Genetic Variant KIAA0825:p.Asn732Lys (chr5-94462437-A-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001145678.3(KIAA0825):c.2196T>A(p.Asn732Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000268 in 1,494,592 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00047 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 2 hom. )

Consequence

KIAA0825
NM_001145678.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.20

Publications

2 publications found

Variant links:

Genes affected

KIAA0825 (HGNC:28532): (KIAA0825)

KIAA0825 Gene-Disease associations (from GenCC):

polydactyly, postaxial, type a10
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
postaxial polydactyly type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

KIAA0825 links:

ENSG00000309437 (HGNC:):

ENSG00000309437 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011537105).

BP6

Variant 5-94462437-A-T is Benign according to our data. Variant chr5-94462437-A-T is described in ClinVar as Benign. ClinVar VariationId is 3048701.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145678.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIAA0825	NM_001145678.3	MANE Select	c.2196T>A	p.Asn732Lys	missense	Exon 12 of 21	NP_001139150.1	A0A804HHT9
KIAA0825	NM_001385712.1		c.2196T>A	p.Asn732Lys	missense	Exon 13 of 22	NP_001372641.1	A0A994J718
KIAA0825	NM_001388325.1		c.2196T>A	p.Asn732Lys	missense	Exon 12 of 21	NP_001375254.1	A0A994J718

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIAA0825	ENST00000682413.1	MANE Select	c.2196T>A	p.Asn732Lys	missense	Exon 12 of 21	ENSP00000506760.1	A0A804HHT9
KIAA0825	ENST00000504117.1	TSL:1	n.1043T>A		non_coding_transcript_exon	Exon 6 of 9
KIAA0825	ENST00000703867.1		c.2196T>A	p.Asn732Lys	missense	Exon 12 of 21	ENSP00000515512.1	A0A994J718

Frequencies

GnomAD3 genomes

AF:

0.000474

AC:

AN:

151938

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0135

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00101

AC:

153

AN:

150962

AF XY:

0.000875

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0141

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000236

GnomAD4 exome

AF:

0.000245

AC:

329

AN:

1342536

Hom.:

Cov.:

AF XY:

0.000238

AC XY:

158

AN XY:

664344

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30226

American (AMR)

AF:

0.00

AC:

AN:

34638

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24562

East Asian (EAS)

AF:

0.00860

AC:

303

AN:

35248

South Asian (SAS)

AF:

0.0000654

AC:

AN:

76510

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49114

Middle Eastern (MID)

AF:

0.000368

AC:

AN:

5430

European-Non Finnish (NFE)

AF:

0.00000194

AC:

AN:

1030688

Other (OTH)

AF:

0.000303

AC:

AN:

56120

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000474

AC:

AN:

152056

Hom.:

Cov.:

AF XY:

0.000565

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41574

American (AMR)

AF:

0.0000655

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.0135

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67814

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000427

Hom.:

Bravo

AF:

0.000499

ExAC

AF:

0.000167

AC:

Asia WGS

AF:

0.00145

AC:

AN:

3474

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

KIAA0825-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

Eigen

Benign

0.18

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.78

M_CAP

Benign

0.032

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.6

PhyloP100

2.2

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.98

REVEL

Benign

0.16

Sift

Benign

0.14

Sift4G

Uncertain

0.022

Polyphen

1.0

Vest4

0.42

MutPred

0.52

Gain of methylation at N732 (P = 0.0206)

MVP

0.29

ClinPred

0.080

GERP RS

3.1

Varity_R

0.074

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over