Genetic Variant NM_019590.5:c.2659G>A (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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1217	NM_019590.5 link	c.2659G>A	p.Ala887Thr	missense_variant	Exon 13 of 21	ENST00000376454.8	NP_062536.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1217	ENST00000376454.8 link	c.2659G>A	p.Ala887Thr	missense_variant	Exon 13 of 21	1	NM_019590.5	ENSP00000365637.3

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 v4.3

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

.;T;.;.;.;T;.;.;.;.;.

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.73

.;T;T;T;T;T;T;T;T;T;T

MetaRNN

Benign

0.0076

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

.;.;.;.;.;L;.;.;.;.;.

PhyloP100

4.5

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.97

N;N;N;N;.;N;N;N;N;N;N

REVEL

Benign

0.087

Sift

Benign

0.18

T;T;T;.;.;T;T;T;T;T;T

Sift4G

Benign

0.22

T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.086, 0.14, 0.17, 0.10, 0.44

.;.;B;.;.;B;.;B;B;B;B

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over