chr17-6623016-G-C

Position:

• chr17-6623016-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS1

The NM_014804.3(KIAA0753):​c.970C>G​(p.Arg324Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000431 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: KIAA0753 NM_014804.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.78

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09272072).
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0000431 (63/1461850) while in subpopulation SAS AF= 0.000626 (54/86258). AF 95% confidence interval is 0.000492. There are 0 homozygotes in gnomad4_exome. There are 42 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0753	NM_014804.3	c.970C>G	p.Arg324Gly	missense_variant	6/19	ENST00000361413.8	NP_055619.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0753	ENST00000361413.8	c.970C>G	p.Arg324Gly	missense_variant	6/19	1	NM_014804.3	ENSP00000355250.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000722 AC: 18 AN: 249202 Hom.: 0 AF XY: 0.0000888 AC XY: 12 AN XY: 135208

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000431 AC: 63 AN: 1461850 Hom.: 0 Cov.: 31 AF XY: 0.0000578 AC XY: 42 AN XY: 727234

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000626

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000993

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000910 AC: 11

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.013	T;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.64
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.093	T;T
MetaSVM	Benign	-0.61	T
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.4	N;.
REVEL	Benign	0.28
Sift	Benign	0.071	T;.
Sift4G	Benign	0.17	T;T
Polyphen		0.025	B;.
Vest4		0.30
MutPred		0.35		Gain of relative solvent accessibility (P = 0.0479);.;
MVP		0.46
MPC		0.13
ClinPred		0.074	T
GERP RS		-0.032
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.099
gMVP		0.032

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: rs746068882; hg19: chr17-6526336; COSMIC: COSV63817185; COSMIC: COSV63817185;