6-109155803-C-T

Variant names:

• chr6-109155803-C-T
• NM_001271852.3:c.670C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001271852.3(CEP57L1):​c.670C>T​(p.Leu224Phe) 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. 15/21 in silico tools predict 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: 32)
• Consequence: CEP57L1 NM_001271852.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.459

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23356098).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP57L1	NM_001271852.3	c.670C>T	p.Leu224Phe	missense_variant	Exon 7 of 11	ENST00000517392.6	NP_001258781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP57L1	ENST00000517392.6	c.670C>T	p.Leu224Phe	missense_variant	Exon 7 of 11	2	NM_001271852.3	ENSP00000427844.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 23

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.670C>T (p.L224F) alteration is located in exon 9 (coding exon 6) of the CEP57L1 gene. This alteration results from a C to T substitution at nucleotide position 670, causing the leucine (L) at amino acid position 224 to be replaced by a phenylalanine (F). 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	Benign	0.16
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T;T;T;T;T;.;.;.;T;T;T;T;.
Eigen	Benign	-0.098
Eigen_PC	Benign	0.016
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.85	T;.;T;T;.;T;T;D;T;T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.23	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.4	.;L;.;.;.;L;.;.;.;.;.;L;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.7	N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.094
Sift	Benign	0.14	T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.32	T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.28	B;B;B;.;B;.;.;.;.;.;.;B;.
Vest4		0.19
MutPred		0.63		.;Loss of MoRF binding (P = 0.1284);Loss of MoRF binding (P = 0.1284);Loss of MoRF binding (P = 0.1284);Loss of MoRF binding (P = 0.1284);Loss of MoRF binding (P = 0.1284);.;.;Loss of MoRF binding (P = 0.1284);.;.;Loss of MoRF binding (P = 0.1284);.;
MVP		0.66
MPC		0.12
ClinPred		0.78	D
GERP RS		4.3
Varity_R		0.092
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-109477006;