6-109150204-G-C

Variant names:

• chr6-109150204-G-C
• rs369697487
• NM_001271852.3:c.427G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001271852.3(CEP57L1):​c.427G>C​(p.Val143Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CEP57L1 NM_001271852.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.68

Genes affected

CEP57L1 (HGNC:21561): (centrosomal protein 57 like 1) Enables identical protein binding activity. Predicted to be located in cytoplasm and microtubule. Predicted to be active in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31992507).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP57L1	NM_001271852.3	c.427G>C	p.Val143Leu	missense_variant	Exon 4 of 11	ENST00000517392.6	NP_001258781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP57L1	ENST00000517392.6	c.427G>C	p.Val143Leu	missense_variant	Exon 4 of 11	2	NM_001271852.3	ENSP00000427844.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	T;T;T;T;T;.;T;.;T;.;.;.;T;T;T;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D;.;D;D;D;D;D;D;.;D;D;D;D;D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.32	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	.;N;.;.;.;.;.;.;.;N;.;.;.;.;.;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.7	N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.027	D;D;D;D;D;D;D;D;D;D;D;D;D;T;D;D
Sift4G	Benign	0.14	T;D;D;D;D;D;D;T;D;D;T;T;D;T;D;D
Polyphen		0.64	P;P;P;.;.;.;.;.;P;.;.;.;.;.;.;P
Vest4		0.42
MutPred		0.48		.;Loss of methylation at K147 (P = 0.0757);Loss of methylation at K147 (P = 0.0757);Loss of methylation at K147 (P = 0.0757);Loss of methylation at K147 (P = 0.0757);Loss of methylation at K147 (P = 0.0757);Loss of methylation at K147 (P = 0.0757);.;Loss of methylation at K147 (P = 0.0757);Loss of methylation at K147 (P = 0.0757);.;.;Loss of methylation at K147 (P = 0.0757);.;.;Loss of methylation at K147 (P = 0.0757);
MVP		0.41
MPC		0.19
ClinPred		0.94	D
GERP RS		5.3
Varity_R		0.38
gMVP		0.28

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: rs369697487; hg19: chr6-109471407;