17-6589787-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014804.3(KIAA0753):c.2778A>G(p.Ile926Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.022 in 1,600,498 control chromosomes in the GnomAD database, including 481 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (36 hom., cov: 33)
  • Exomes 𝑓: 0.023 (445 hom.)
• Consequence: KIAA0753 NM_014804.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.376

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038268864).
• BP6: Variant 17-6589787-T-C is Benign according to our data. Variant chr17-6589787-T-C is described in ClinVar as [Benign]. Clinvar id is 1667710.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0155 (2358/152318) while in subpopulation SAS AF= 0.0329 (159/4832). AF 95% confidence interval is 0.0287. There are 36 homozygotes in gnomad4. There are 1156 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0753	NM_014804.3	c.2778A>G	p.Ile926Met	missense_variant	18/19	ENST00000361413.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0753	ENST00000361413.8	c.2778A>G	p.Ile926Met	missense_variant	18/19	1	NM_014804.3	P1

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2357 AN: 152200 Hom.: 36 Cov.: 33

Gnomad AFR AF: 0.00384

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00890

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0325

Gnomad FIN AF: 0.0267

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0215

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.0185 AC: 4343 AN: 235284 Hom.: 62 AF XY: 0.0200 AC XY: 2557 AN XY: 127782

Gnomad AFR exome AF: 0.00369

Gnomad AMR exome AF: 0.00557

Gnomad ASJ exome AF: 0.0366

Gnomad EAS exome AF: 0.0000584

Gnomad SAS exome AF: 0.0298

Gnomad FIN exome AF: 0.0231

Gnomad NFE exome AF: 0.0216

Gnomad OTH exome AF: 0.0187

GnomAD4 exome AF: 0.0227 AC: 32897 AN: 1448180 Hom.: 445 Cov.: 31 AF XY: 0.0229 AC XY: 16521 AN XY: 720372

Gnomad4 AFR exome AF: 0.00352

Gnomad4 AMR exome AF: 0.00570

Gnomad4 ASJ exome AF: 0.0376

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.0303

Gnomad4 FIN exome AF: 0.0259

Gnomad4 NFE exome AF: 0.0238

Gnomad4 OTH exome AF: 0.0211

GnomAD4 genome AF: 0.0155 AC: 2358 AN: 152318 Hom.: 36 Cov.: 33 AF XY: 0.0155 AC XY: 1156 AN XY: 74484

Gnomad4 AFR AF: 0.00383

Gnomad4 AMR AF: 0.00882

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0329

Gnomad4 FIN AF: 0.0267

Gnomad4 NFE AF: 0.0215

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.0213 Hom.: 60

Bravo AF: 0.0132

TwinsUK AF: 0.0278 AC: 103

ALSPAC AF: 0.0210 AC: 81

ESP6500AA AF: 0.00551 AC: 21

ESP6500EA AF: 0.0247 AC: 203

ExAC AF: 0.0185 AC: 2230

Asia WGS AF: 0.0150 AC: 53 AN: 3478

EpiCase AF: 0.0214

EpiControl AF: 0.0195

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	17
Dann	Uncertain	0.99
DEOGEN2	Benign	0.035	T;T;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.63	T;T;T
MetaRNN	Benign	0.0038	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.75	N;N;N;N
PrimateAI	Benign	0.41	T
Sift4G	Benign	0.17	T;T;T
Polyphen		0.26	.;B;.
Vest4		0.11, 0.088
MPC		0.28
ClinPred		0.022	T
GERP RS		-7.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.057
gMVP		0.40

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

LitVar

Other links and lift over

dbSNP: rs61735435; hg19: chr17-6493107;