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. The variant received 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
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014895.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP162	NM_014895.4	MANE Select	c.3848G>T	p.Arg1283Leu	missense	Exon 25 of 27	NP_055710.2	Q5TB80-1
	CEP162	NM_001286206.2		c.3620G>T	p.Arg1207Leu	missense	Exon 25 of 27	NP_001273135.1	Q5TB80-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP162	ENST00000403245.8	TSL:5 MANE Select	c.3848G>T	p.Arg1283Leu	missense	Exon 25 of 27	ENSP00000385215.3	Q5TB80-1
	CEP162	ENST00000257766.8	TSL:1	c.3620G>T	p.Arg1207Leu	missense	Exon 25 of 27	ENSP00000257766.4	Q5TB80-2
	CEP162	ENST00000962927.1		c.3848G>T	p.Arg1283Leu	missense	Exon 25 of 27	ENSP00000632986.1

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32414

American (AMR) AF: 0.00 AC: 0 AN: 37874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25158

East Asian (EAS) AF: 0.0000519 AC: 2 AN: 38554

South Asian (SAS) AF: 0.00 AC: 0 AN: 78736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5634

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088650

Other (OTH) AF: 0.00 AC: 0 AN: 58632

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.063	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.3
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.061	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
Mutation Taster		=27/73	disease causing

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

Other links and lift over

dbSNP: rs865999990; hg19: chr6-84856428;