chr6-84146709-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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 (★). Synonymous variant affecting the same amino acid position (i.e. R1283R) has been classified 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
• 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 2 ACMG points.

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

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>A	p.Arg1283Gln	missense	Exon 25 of 27	NP_055710.2	Q5TB80-1
	CEP162	NM_001286206.2		c.3620G>A	p.Arg1207Gln	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>A	p.Arg1283Gln	missense	Exon 25 of 27	ENSP00000385215.3	Q5TB80-1
	CEP162	ENST00000257766.8	TSL:1	c.3620G>A	p.Arg1207Gln	missense	Exon 25 of 27	ENSP00000257766.4	Q5TB80-2
	CEP162	ENST00000962927.1		c.3848G>A	p.Arg1283Gln	missense	Exon 25 of 27	ENSP00000632986.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 201118 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

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

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: 0.000104 AC: 4 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: 0.00000459 AC: 5 AN: 1088650

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

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.3
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.23
Sift	Uncertain	0.013	D
Sift4G	Benign	0.071	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
Mutation Taster		=55/45	polymorphism

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

Other links and lift over

dbSNP: rs865999990; hg19: chr6-84856428;