Genetic Variant KIAA1217:p.Ala887Thr (chr10-24524525-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019590.5(KIAA1217):c.2659G>A(p.Ala887Thr) variant causes a missense change. The variant allele was found at a frequency of 0.254 in 1,613,792 control chromosomes in the GnomAD database, including 54,454 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 4937 hom., cov: 32)

Exomes 𝑓: 0.25 ( 49517 hom. )

Consequence

KIAA1217
NM_019590.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.47

Publications

32 publications found

Variant links:

Genes affected

KIAA1217 (HGNC:25428): (KIAA1217) Predicted to be involved in embryonic skeletal system development. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

KIAA1217 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007587403).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019590.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KIAA1217	NM_019590.5	MANE Select	c.2659G>A	p.Ala887Thr	missense	Exon 13 of 21	NP_062536.2
KIAA1217	NM_001282767.2		c.2554G>A	p.Ala852Thr	missense	Exon 12 of 19	NP_001269696.1
KIAA1217	NM_001282768.2		c.2554G>A	p.Ala852Thr	missense	Exon 12 of 18	NP_001269697.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KIAA1217	ENST00000376454.8	TSL:1 MANE Select	c.2659G>A	p.Ala887Thr	missense	Exon 13 of 21	ENSP00000365637.3
KIAA1217	ENST00000376451.4	TSL:1	c.1708G>A	p.Ala570Thr	missense	Exon 8 of 15	ENSP00000365634.2
KIAA1217	ENST00000376452.7	TSL:1	c.2554G>A	p.Ala852Thr	missense	Exon 12 of 19	ENSP00000365635.3

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37681

AN:

151966

Hom.:

4939

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.410

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.290

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.277

Gnomad OTH

AF:

0.288

GnomAD2 exomes

AF:

0.224

AC:

56132

AN:

250896

AF XY:

0.226

show subpopulations

Gnomad AFR exome

AF:

0.231

Gnomad AMR exome

AF:

0.170

Gnomad ASJ exome

AF:

0.287

Gnomad EAS exome

AF:

0.103

Gnomad FIN exome

AF:

0.203

Gnomad NFE exome

AF:

0.279

Gnomad OTH exome

AF:

0.263

GnomAD4 exome

AF:

0.255

AC:

372572

AN:

1461708

Hom.:

49517

Cov.:

AF XY:

0.252

AC XY:

183406

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.237

AC:

7931

AN:

33480

American (AMR)

AF:

0.181

AC:

8115

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

7620

AN:

26136

East Asian (EAS)

AF:

0.103

AC:

4076

AN:

39698

South Asian (SAS)

AF:

0.140

AC:

12075

AN:

86256

European-Finnish (FIN)

AF:

0.205

AC:

10948

AN:

53304

Middle Eastern (MID)

AF:

0.286

AC:

1650

AN:

5768

European-Non Finnish (NFE)

AF:

0.274

AC:

305164

AN:

1111956

Other (OTH)

AF:

0.248

AC:

14993

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

18071

36143

54214

72286

90357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10018

20036

30054

40072

50090

<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:

0.248

AC:

37681

AN:

152084

Hom.:

4937

Cov.:

AF XY:

0.242

AC XY:

18017

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.235

AC:

9748

AN:

41482

American (AMR)

AF:

0.242

AC:

3696

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

1006

AN:

3470

East Asian (EAS)

AF:

0.112

AC:

577

AN:

5160

South Asian (SAS)

AF:

0.135

AC:

653

AN:

4822

European-Finnish (FIN)

AF:

0.202

AC:

2135

AN:

10580

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.277

AC:

18794

AN:

67964

Other (OTH)

AF:

0.284

AC:

600

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1452

2904

4355

5807

7259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.269

Hom.:

26440

Bravo

AF:

0.254

TwinsUK

AF:

0.262

AC:

971

ALSPAC

AF:

0.265

AC:

1022

ESP6500AA

AF:

0.237

AC:

1043

ESP6500EA

AF:

0.288

AC:

2478

ExAC

AF:

0.226

AC:

27446

Asia WGS

AF:

0.137

AC:

481

AN:

3478

EpiCase

AF:

0.296

EpiControl

AF:

0.297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0076

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

4.5

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.97

REVEL

Benign

0.087

Sift

Benign

0.18

Sift4G

Benign

0.22

Polyphen

0.086

Vest4

0.048

MPC

0.13

ClinPred

0.011

GERP RS

4.6

Varity_R

0.049

gMVP

0.30

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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