rs865999990

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-84146709-C-A
• chr6-84146709-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014895.4(CEP162):​c.3848G>T​(p.Arg1283Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,417,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R1283Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CEP162 NM_014895.4 missense
• Clinical Significance: Not reported in ClinVar
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.747

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP162	NM_014895.4	c.3848G>T	p.Arg1283Leu	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>T	p.Arg1283Leu	missense_variant	Exon 25 of 27	5	NM_014895.4	ENSP00000385215.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1417052 Hom.: 0 Cov.: 27 AF XY: 0.00000142 AC XY: 1 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: 0.0000519

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	.;T;.
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	.;D;D
M_CAP	Benign	0.063	D
MetaRNN	Pathogenic	0.75	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	.;M;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.6	D;D;.
REVEL	Uncertain	0.39
Sift	Uncertain	0.0050	D;D;.
Sift4G	Benign	0.061	T;D;T
Polyphen		0.94	.;P;.
Vest4		0.80
MutPred		0.33		.;Loss of loop (P = 0.1258);.;
MVP		0.29
MPC		0.11
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.49
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;