Genetic Variant NM_014804.3:c.2338C>A (chr17-6596178-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014804.3(KIAA0753):c.2338C>A(p.Arg780Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,526 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R780C) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KIAA0753
NM_014804.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.30

Publications

6 publications found

Variant links:

Genes affected

KIAA0753 (HGNC:29110): (KIAA0753) This gene encodes a subunit of a protein complex that regulates ciliogenesis and cilia maintenance. The encoded protein has also been shown to regulate centriolar duplication. Mutations in this gene cause an orofaciodigital syndrome and a form of Joubert syndrome in human patients. [provided by RefSeq, May 2017]

KIAA0753 Gene-Disease associations (from GenCC):

orofaciodigital syndrome XV
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Jeune syndrome
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Franklin by Genoox
orofaciodigital syndrome type 6
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

KIAA0753 links:

ENSG00000282936 (HGNC:):

ENSG00000282936 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14722294).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014804.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KIAA0753	NM_014804.3	MANE Select	c.2338C>A	p.Arg780Ser	missense	Exon 15 of 19	NP_055619.2
KIAA0753	NM_001351225.2		c.1441C>A	p.Arg481Ser	missense	Exon 15 of 19	NP_001338154.1
KIAA0753	NR_147086.2		n.2144C>A		non_coding_transcript_exon	Exon 13 of 17

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KIAA0753	ENST00000361413.8	TSL:1 MANE Select	c.2338C>A	p.Arg780Ser	missense	Exon 15 of 19	ENSP00000355250.3
KIAA0753	ENST00000572370.5	TSL:2	c.1441C>A	p.Arg481Ser	missense	Exon 14 of 18	ENSP00000460050.1
KIAA0753	ENST00000542826.6	TSL:2	n.*776C>A		non_coding_transcript_exon	Exon 8 of 12	ENSP00000444946.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248982

AF XY:

0.00000740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461526

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727064

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111734

Other (OTH)

AF:

0.00

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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

Cov.:

ExAC

AF:

0.00000827

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0023

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.36

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.71

M_CAP

Benign

0.0091

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

PhyloP100

1.3

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.90

REVEL

Benign

0.027

Sift

Benign

0.13

Sift4G

Benign

0.15

Polyphen

0.16

Vest4

0.23

MutPred

0.40

Gain of phosphorylation at R780 (P = 0.009)

MVP

0.31

MPC

0.11

ClinPred

0.15

GERP RS

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.067

gMVP

0.17

Mutation Taster

=99/1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over