Genetic Variant KIAA0825:p.Asn1151Ser (chr5-94391539-T-C) – 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.3452A>G(p.Asn1151Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00023 in 1,549,718 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 2 hom. )

Consequence

KIAA0825
NM_001145678.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.53

Publications

1 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:

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=0.009839088).

BP6

Variant 5-94391539-T-C is Benign according to our data. Variant chr5-94391539-T-C is described in ClinVar as Benign. ClinVar VariationId is 3035003.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.3452A>G	p.Asn1151Ser	missense	Exon 18 of 21	NP_001139150.1	A0A804HHT9
KIAA0825	NM_001385712.1		c.3467A>G	p.Asn1156Ser	missense	Exon 19 of 22	NP_001372641.1	A0A994J718
KIAA0825	NM_001388325.1		c.3467A>G	p.Asn1156Ser	missense	Exon 18 of 21	NP_001375254.1	A0A994J718

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIAA0825	ENST00000682413.1	MANE Select	c.3452A>G	p.Asn1151Ser	missense	Exon 18 of 21	ENSP00000506760.1	A0A804HHT9
KIAA0825	ENST00000703867.1		c.3467A>G	p.Asn1156Ser	missense	Exon 18 of 21	ENSP00000515512.1	A0A994J718
KIAA0825	ENST00000513200.7	TSL:5	c.3452A>G	p.Asn1151Ser	missense	Exon 17 of 20	ENSP00000424618.2	Q8IV33-1

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0102

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000864

AC:

135

AN:

156224

AF XY:

0.000785

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0120

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000456

GnomAD4 exome

AF:

0.000210

AC:

294

AN:

1397542

Hom.:

Cov.:

AF XY:

0.000196

AC XY:

135

AN XY:

689314

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31590

American (AMR)

AF:

0.0000560

AC:

AN:

35692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25158

East Asian (EAS)

AF:

0.00621

AC:

222

AN:

35730

South Asian (SAS)

AF:

0.0000757

AC:

AN:

79230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49270

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.00000743

AC:

AN:

1077250

Other (OTH)

AF:

0.000949

AC:

AN:

57928

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

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:

0.000407

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41568

American (AMR)

AF:

0.000327

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0104

AC:

AN:

5184

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67910

Other (OTH)

AF:

0.000473

AC:

AN:

2116

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

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:

0.000208

Hom.:

Bravo

AF:

0.000408

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000431

AC:

Asia WGS

AF:

0.00202

AC:

AN:

3478

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

Benign

0.24

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0098

MetaSVM

Uncertain

-0.021

MutationAssessor

Uncertain

2.7

PhyloP100

7.5

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.75

MVP

0.74

ClinPred

0.11

GERP RS

5.2

Varity_R

0.26

Mutation Taster

=74/26

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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