12-94308904-T-A

Position:

• chr12-94308904-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016122.3(CEP83):​c.2015A>T​(p.Gln672Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Q672Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP83 NM_016122.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.90

Genes affected

CEP83 (HGNC:17966): (centrosomal protein 83) The protein encoded by this gene is a centriolar protein involved in primary cilium assembly. Defects in this gene have been associated with infantile nephronophthisis and intellectual disability. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP83	NM_016122.3	c.2015A>T	p.Gln672Leu	missense_variant	17/17	ENST00000397809.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP83	ENST00000397809.10	c.2015A>T	p.Gln672Leu	missense_variant	17/17	1	NM_016122.3	P1
CEP83	ENST00000339839.9	c.2015A>T	p.Gln672Leu	missense_variant	16/16	1		P1
CEP83	ENST00000552632.5	c.407A>T	p.Gln136Leu	missense_variant	4/5	3
CEP83	ENST00000546783.1	n.469A>T		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2022

The c.2015A>T (p.Q672L) alteration is located in exon 17 (coding exon 15) of the CEP83 gene. This alteration results from a A to T substitution at nucleotide position 2015, causing the glutamine (Q) at amino acid position 672 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	28
DANN	Uncertain	0.99
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.79	T;.;T
M_CAP	Benign	0.071	D
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Benign	-0.58	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-4.4	D;D;D
REVEL	Benign	0.26
Sift	Uncertain	0.0060	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.54, 0.55
MVP		0.75
MPC		0.44
ClinPred		0.97	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-94702680;