6-109155302-T-C

Variant names:

• chr6-109155302-T-C
• rs1773105824
• NM_001271852.3:c.652T>C

Variant summary

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

The NM_001271852.3(CEP57L1):​c.652T>C​(p.Ser218Pro) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CEP57L1 NM_001271852.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.78

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=0.3404138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP57L1	NM_001271852.3	c.652T>C	p.Ser218Pro	missense_variant	Exon 6 of 11	ENST00000517392.6	NP_001258781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP57L1	ENST00000517392.6	c.652T>C	p.Ser218Pro	missense_variant	Exon 6 of 11	2	NM_001271852.3	ENSP00000427844.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.07e-7 AC: 1 AN: 1414518 Hom.: 0 Cov.: 23 AF XY: 0.00000142 AC XY: 1 AN XY: 704592

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000260

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 03, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.652T>C (p.S218P) alteration is located in exon 8 (coding exon 5) of the CEP57L1 gene. This alteration results from a T to C substitution at nucleotide position 652, causing the serine (S) at amino acid position 218 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	T;T;T;T;.;T;.;.;.;T;T;T;T
Eigen	Benign	-0.096
Eigen_PC	Benign	-0.044
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.74	T;.;D;D;T;.;D;D;D;T;D;D;D
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.34	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.69	.;N;.;.;.;.;N;.;.;.;.;.;N
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.5	N;N;N;N;N;N;N;N;D;N;N;N;N
REVEL	Uncertain	0.30
Sift	Uncertain	0.011	D;T;T;D;T;D;D;D;D;D;D;D;T
Sift4G	Benign	0.079	T;D;T;T;T;T;D;D;D;D;T;D;D
Polyphen		0.75	P;P;P;.;.;P;.;.;.;.;.;.;P
Vest4		0.34
MutPred		0.45		.;Loss of phosphorylation at S218 (P = 0.0855);Loss of phosphorylation at S218 (P = 0.0855);Loss of phosphorylation at S218 (P = 0.0855);Loss of phosphorylation at S218 (P = 0.0855);Loss of phosphorylation at S218 (P = 0.0855);Loss of phosphorylation at S218 (P = 0.0855);.;.;Loss of phosphorylation at S218 (P = 0.0855);.;.;Loss of phosphorylation at S218 (P = 0.0855);
MVP		0.77
MPC		0.26
ClinPred		0.65	D
GERP RS		1.2
Varity_R		0.51
gMVP		0.36

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: rs1773105824; hg19: chr6-109476505;