Variant 6-109146758-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001271852.3(CEP57L1):c.161C>G(p.Ala54Gly) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CEP57L1
NM_001271852.3 missense, splice_region

Scores

Splicing: ADA: 0.6669

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.43

Variant links:

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]

CEP57L1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP57L1	NM_001271852.3 linkuse as main transcript	c.161C>G	p.Ala54Gly	missense_variant, splice_region_variant	3/11	ENST00000517392.6	NP_001258781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP57L1	ENST00000517392.6 linkuse as main transcript	c.161C>G	p.Ala54Gly	missense_variant, splice_region_variant	3/11	2	NM_001271852.3	ENSP00000427844		Q8IYX8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000529

AC:

AN:

188998

Hom.:

AF XY:

0.00000963

AC XY:

AN XY:

103880

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000111

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.15e-7

AC:

AN:

1398454

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

694024

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.20e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 16, 2024

The c.161C>G (p.A54G) alteration is located in exon 5 (coding exon 2) of the CEP57L1 gene. This alteration results from a C to G substitution at nucleotide position 161, causing the alanine (A) at amino acid position 54 to be replaced by a glycine (G). 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

Uncertain

0.35

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;T;T;T;T;.;T;T;T;T;.;T;T;T

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;.;D;D;D;D;D;D;D;.;D;D;D;D

M_CAP

Benign

0.074

MetaRNN

Uncertain

0.43

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.34

MutationAssessor

Uncertain

2.7

.;M;.;.;.;.;.;.;.;.;M;.;.;M

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.5

D;D;D;D;D;D;D;D;D;D;D;D;D;D

REVEL

Benign

0.27

Sift

Uncertain

0.0030

D;D;D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.015

D;D;D;D;D;D;D;T;T;D;D;D;D;D

Polyphen

1.0

D;D;D;.;.;.;.;.;.;D;.;.;.;D

Vest4

0.66

MutPred

0.14

Gain of catalytic residue at P50 (P = 0.0696);Gain of catalytic residue at P50 (P = 0.0696);Gain of catalytic residue at P50 (P = 0.0696);Gain of catalytic residue at P50 (P = 0.0696);Gain of catalytic residue at P50 (P = 0.0696);Gain of catalytic residue at P50 (P = 0.0696);Gain of catalytic residue at P50 (P = 0.0696);Gain of catalytic residue at P50 (P = 0.0696);Gain of catalytic residue at P50 (P = 0.0696);Gain of catalytic residue at P50 (P = 0.0696);Gain of catalytic residue at P50 (P = 0.0696);Gain of catalytic residue at P50 (P = 0.0696);.;Gain of catalytic residue at P50 (P = 0.0696);

MVP

0.74

MPC

0.30

ClinPred

0.94

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.46

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.67

dbscSNV1_RF

Benign

0.49

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over