Genetic Variant NM_019590.5:c.926C>T (chr10-24473307-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_019590.5(KIAA1217):c.926C>T(p.Ala309Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000296 in 1,556,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

KIAA1217
NM_019590.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.50

Publications

7 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0537706).

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.926C>T	p.Ala309Val	missense	Exon 6 of 21	NP_062536.2
KIAA1217	NM_001282767.2		c.926C>T	p.Ala309Val	missense	Exon 6 of 19	NP_001269696.1	Q5T5P2-10
KIAA1217	NM_001282768.2		c.926C>T	p.Ala309Val	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.926C>T	p.Ala309Val	missense	Exon 6 of 21	ENSP00000365637.3	Q5T5P2-1
KIAA1217	ENST00000376451.4	TSL:1	c.80C>T	p.Ala27Val	missense	Exon 2 of 15	ENSP00000365634.2	Q5T5P2-3
KIAA1217	ENST00000376452.7	TSL:1	c.926C>T	p.Ala309Val	missense	Exon 6 of 19	ENSP00000365635.3	Q5T5P2-10

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000437

AC:

AN:

205804

AF XY:

0.0000368

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000208

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000571

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000209

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000292

AC:

AN:

1403910

Hom.:

Cov.:

AF XY:

0.0000217

AC XY:

AN XY:

691330

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31908

American (AMR)

AF:

0.000183

AC:

AN:

38258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21906

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39222

South Asian (SAS)

AF:

0.0000531

AC:

AN:

75282

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50786

Middle Eastern (MID)

AF:

0.000366

AC:

AN:

5462

European-Non Finnish (NFE)

AF:

0.0000240

AC:

AN:

1083242

Other (OTH)

AF:

0.0000173

AC:

AN:

57844

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

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:

0.0000329

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41420

American (AMR)

AF:

0.00

AC:

AN:

15280

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:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

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:

0.00

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000496

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

Benign

0.069

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.51

CADD

Benign

4.6

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.021

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.76

M_CAP

Benign

0.012

MetaRNN

Benign

0.054

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

1.5

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.84

REVEL

Benign

0.069

Sift

Benign

0.30

Sift4G

Benign

0.41

Polyphen

0.15

Vest4

0.10

MutPred

0.097

Loss of relative solvent accessibility (P = 0.0793)

MVP

0.34

MPC

0.16

ClinPred

0.053

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

gMVP

0.28

Mutation Taster

=94/6

polymorphism

(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

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