Genetic Variant KIAA1217:p.Gly292Arg (chr10-24473255-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_019590.5(KIAA1217):c.874G>A(p.Gly292Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,517,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

KIAA1217
NM_019590.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020934075).

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	UniProt
KIAA1217	NM_019590.5	MANE Select	c.874G>A	p.Gly292Arg	missense	Exon 6 of 21	NP_062536.2
KIAA1217	NM_001282767.2		c.874G>A	p.Gly292Arg	missense	Exon 6 of 19	NP_001269696.1	Q5T5P2-10
KIAA1217	NM_001282768.2		c.874G>A	p.Gly292Arg	missense	Exon 6 of 18	NP_001269697.1	Q5T5P2-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIAA1217	ENST00000376454.8	TSL:1 MANE Select	c.874G>A	p.Gly292Arg	missense	Exon 6 of 21	ENSP00000365637.3	Q5T5P2-1
KIAA1217	ENST00000376451.4	TSL:1	c.28G>A	p.Gly10Arg	missense	Exon 2 of 15	ENSP00000365634.2	Q5T5P2-3
KIAA1217	ENST00000376452.7	TSL:1	c.874G>A	p.Gly292Arg	missense	Exon 6 of 19	ENSP00000365635.3	Q5T5P2-10

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000450

AC:

AN:

177584

AF XY:

0.0000751

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.0000146

AC:

AN:

1365474

Hom.:

Cov.:

AF XY:

0.0000164

AC XY:

AN XY:

668814

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30190

American (AMR)

AF:

0.000277

AC:

AN:

28866

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19870

East Asian (EAS)

AF:

0.00

AC:

AN:

38880

South Asian (SAS)

AF:

0.00

AC:

AN:

70066

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49864

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5290

European-Non Finnish (NFE)

AF:

0.00000469

AC:

AN:

1066292

Other (OTH)

AF:

0.000125

AC:

AN:

56156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41554

American (AMR)

AF:

0.000849

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000306

ExAC

AF:

0.0000254

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Benign

0.13

DEOGEN2

Benign

0.0034

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.045

MetaRNN

Benign

0.021

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.0

PhyloP100

1.9

PrimateAI

Uncertain

0.55

PROVEAN

Benign

2.2

REVEL

Benign

0.065

Sift

Benign

0.44

Sift4G

Benign

1.0

Polyphen

0.28

Vest4

0.11

MutPred

0.29

Gain of MoRF binding (P = 0.011)

MVP

0.52

MPC

0.62

ClinPred

0.073

GERP RS

4.8

Varity_R

0.097

gMVP

0.41

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over