6-84146709-C-T

Variant names:

• chr6-84146709-C-T
• rs865999990
• NM_014895.4:c.3848G>A

Variant summary

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

The NM_014895.4(CEP162):​c.3848G>A​(p.Arg1283Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000635 in 1,417,052 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: CEP162 NM_014895.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.28

Genes affected

CEP162 (HGNC:21107): (centrosomal protein 162) Involved in cilium assembly. Located in axonemal microtubule; centriole; and centrosome. [provided by Alliance of Genome Resources, Apr 2022]

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 rank	MANE	Protein	UniProt
CEP162	NM_014895.4	c.3848G>A	p.Arg1283Gln	missense_variant	Exon 25 of 27	ENST00000403245.8	NP_055710.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP162	ENST00000403245.8	c.3848G>A	p.Arg1283Gln	missense_variant	Exon 25 of 27	5	NM_014895.4	ENSP00000385215.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000635 AC: 9 AN: 1417052 Hom.: 0 Cov.: 27 AF XY: 0.00000855 AC XY: 6 AN XY: 701972

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000104

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000459

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3848G>A (p.R1283Q) alteration is located in exon 25 (coding exon 24) of the CEP162 gene. This alteration results from a G to A substitution at nucleotide position 3848, causing the arginine (R) at amino acid position 1283 to be replaced by a glutamine (Q). 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	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.17	.;T;.
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	.;D;D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.4	.;M;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.6	N;N;.
REVEL	Benign	0.23
Sift	Uncertain	0.013	D;D;.
Sift4G	Benign	0.071	T;D;T
Polyphen		1.0	.;D;.
Vest4		0.65
MutPred		0.23		.;Gain of loop (P = 0.1081);.;
MVP		0.36
MPC		0.12
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.31
gMVP		0.33

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: rs865999990; hg19: chr6-84856428;