chr1-173803163-C-A

Variant names:

• chr1-173803163-C-A
• rs779634048
• NM_001387287.1:c.763G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001387287.1(CENPL):​c.763G>T​(p.Ala255Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. A255T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CENPL NM_001387287.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• Publications: 3 publications found

Genes affected

CENPL (HGNC:17879): (centromere protein L) CENPL is a subunit of a CENPH (MIM 605607)-CENPI (MIM 300065)-associated centromeric complex that targets CENPA (MIM 117139) to centromeres and is required for proper kinetochore function and mitotic progression (Okada et al., 2006) [PubMed 16622420].[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.077352464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPL	NM_001387287.1	c.763G>T	p.Ala255Ser	missense_variant	Exon 5 of 6	ENST00000682279.1	NP_001374216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPL	ENST00000682279.1	c.763G>T	p.Ala255Ser	missense_variant	Exon 5 of 6		NM_001387287.1	ENSP00000507473.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	.;T;T
Eigen	Benign	0.066
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.80	T;.;T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.077	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.54	.;N;N
PhyloP100		1.5
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.11	N;N;N
REVEL	Benign	0.036
Sift	Benign	0.27	T;T;T
Sift4G	Benign	0.21	T;T;T
Polyphen		0.91	P;B;B
Vest4		0.19
MutPred		0.35		.;Gain of disorder (P = 0.0355);Gain of disorder (P = 0.0355);
MVP		0.25
MPC		0.26
ClinPred		0.74	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.079
gMVP		0.42
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs779634048; hg19: chr1-173772301;