Genetic Variant KIAA1217:p.Thr1562Thr (chr10-24543956-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_019590.5(KIAA1217):c.4686C>T(p.Thr1562Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,613,730 control chromosomes in the GnomAD database, including 26,974 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 4299 hom., cov: 31)

Exomes 𝑓: 0.17 ( 22675 hom. )

Consequence

KIAA1217
NM_019590.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.14

Publications

16 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP7

Synonymous conserved (PhyloP=-3.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1217	NM_019590.5 link	c.4686C>T	p.Thr1562Thr	synonymous_variant	Exon 19 of 21	ENST00000376454.8	NP_062536.2	Q5T5P2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1217	ENST00000376454.8 link	c.4686C>T	p.Thr1562Thr	synonymous_variant	Exon 19 of 21	1	NM_019590.5	ENSP00000365637.3		Q5T5P2-1

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33362

AN:

151822

Hom.:

4286

Cov.:

show subpopulations

Gnomad AFR

AF:

0.330

Gnomad AMI

AF:

0.254

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.404

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.200

GnomAD2 exomes

AF:

0.208

AC:

52220

AN:

251300

AF XY:

0.199

show subpopulations

Gnomad AFR exome

AF:

0.334

Gnomad AMR exome

AF:

0.272

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.429

Gnomad FIN exome

AF:

0.204

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.185

GnomAD4 exome

AF:

0.166

AC:

242616

AN:

1461790

Hom.:

22675

Cov.:

AF XY:

0.165

AC XY:

120276

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.331

AC:

11075

AN:

33474

American (AMR)

AF:

0.263

AC:

11759

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

3255

AN:

26136

East Asian (EAS)

AF:

0.391

AC:

15530

AN:

39700

South Asian (SAS)

AF:

0.198

AC:

17067

AN:

86256

European-Finnish (FIN)

AF:

0.205

AC:

10939

AN:

53388

Middle Eastern (MID)

AF:

0.173

AC:

999

AN:

5766

European-Non Finnish (NFE)

AF:

0.145

AC:

161113

AN:

1111950

Other (OTH)

AF:

0.180

AC:

10879

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

12276

24551

36827

49102

61378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6118

12236

18354

24472

30590

<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:

0.220

AC:

33406

AN:

151940

Hom.:

4299

Cov.:

AF XY:

0.223

AC XY:

16565

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.330

AC:

13671

AN:

41400

American (AMR)

AF:

0.228

AC:

3488

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

452

AN:

3470

East Asian (EAS)

AF:

0.405

AC:

2076

AN:

5128

South Asian (SAS)

AF:

0.218

AC:

1047

AN:

4796

European-Finnish (FIN)

AF:

0.211

AC:

2225

AN:

10568

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.144

AC:

9761

AN:

67972

Other (OTH)

AF:

0.198

AC:

418

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1279

2558

3837

5116

6395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<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:

0.167

Hom.:

8379

Bravo

AF:

0.228

Asia WGS

AF:

0.312

AC:

1083

AN:

3478

EpiCase

AF:

0.132

EpiControl

AF:

0.132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.027

(source)

DANN

Benign

0.54

PhyloP100

-3.1

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