Genetic Variant NM_001271852.3:c.18G>A (chr6-109145239-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001271852.3(CEP57L1):c.18G>A(p.Met6Ile) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M6V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CEP57L1
NM_001271852.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.559

Publications

0 publications found

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 was made for transcript

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=0.07333171).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271852.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEP57L1	NM_001271852.3	MANE Select	c.18G>A	p.Met6Ile	missense	Exon 2 of 11	NP_001258781.1	Q8IYX8-1
CEP57L1	NM_001350654.2		c.18G>A	p.Met6Ile	missense	Exon 2 of 11	NP_001337583.1
CEP57L1	NM_001350655.2		c.18G>A	p.Met6Ile	missense	Exon 3 of 12	NP_001337584.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEP57L1	ENST00000517392.6	TSL:2 MANE Select	c.18G>A	p.Met6Ile	missense	Exon 2 of 11	ENSP00000427844.1	Q8IYX8-1
CEP57L1	ENST00000359793.7	TSL:1	c.18G>A	p.Met6Ile	missense	Exon 2 of 11	ENSP00000352841.3	Q8IYX8-1
CEP57L1	ENST00000368970.6	TSL:5	c.18G>A	p.Met6Ile	missense	Exon 2 of 11	ENSP00000357966.2	E5RFY4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1429842

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712412

African (AFR)

AF:

0.00

AC:

AN:

32532

American (AMR)

AF:

0.00

AC:

AN:

43312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25404

East Asian (EAS)

AF:

0.00

AC:

AN:

39406

South Asian (SAS)

AF:

0.00

AC:

AN:

83834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53016

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4694

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1088534

Other (OTH)

AF:

0.00

AC:

AN:

59110

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.031

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.72

M_CAP

Benign

0.0090

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

0.56

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.6

REVEL

Benign

0.030

Sift

Benign

0.096

Sift4G

Uncertain

0.060

Polyphen

0.072

Vest4

0.17

MutPred

0.18

Loss of disorder (P = 0.0416)

MVP

0.26

MPC

0.045

ClinPred

0.066

GERP RS

2.6

Varity_R

0.15

gMVP

0.33

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over