6-109145249-G-T

Position:

• chr6-109145249-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001271852.3(CEP57L1):​c.28G>T​(p.Val10Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,593,730 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0075 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00073 (12 hom.)
• Consequence: CEP57L1 NM_001271852.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.911

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0058745146).
• BP6: Variant 6-109145249-G-T is Benign according to our data. Variant chr6-109145249-G-T is described in ClinVar as [Benign]. Clinvar id is 788539.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00747 (1135/151890) while in subpopulation AFR AF= 0.0256 (1064/41486). AF 95% confidence interval is 0.0244. There are 11 homozygotes in gnomad4. There are 523 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP57L1	NM_001271852.3	c.28G>T	p.Val10Leu	missense_variant	2/11	ENST00000517392.6	NP_001258781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP57L1	ENST00000517392.6	c.28G>T	p.Val10Leu	missense_variant	2/11	2	NM_001271852.3	ENSP00000427844

Frequencies

GnomAD3 genomes AF: 0.00749 AC: 1137 AN: 151772 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0258

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00368

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00624

GnomAD3 exomes AF: 0.00183 AC: 454 AN: 247880 Hom.: 5 AF XY: 0.00134 AC XY: 180 AN XY: 134090

Gnomad AFR exome AF: 0.0265

Gnomad AMR exome AF: 0.000587

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000892

Gnomad OTH exome AF: 0.000831

GnomAD4 exome AF: 0.000730 AC: 1053 AN: 1441840 Hom.: 12 Cov.: 27 AF XY: 0.000622 AC XY: 447 AN XY: 718414

Gnomad4 AFR exome AF: 0.0276

Gnomad4 AMR exome AF: 0.000944

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000506

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000109

Gnomad4 OTH exome AF: 0.00148

GnomAD4 genome AF: 0.00747 AC: 1135 AN: 151890 Hom.: 11 Cov.: 32 AF XY: 0.00705 AC XY: 523 AN XY: 74224

Gnomad4 AFR AF: 0.0256

Gnomad4 AMR AF: 0.00368

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000295

Gnomad4 OTH AF: 0.00617

Alfa AF: 0.000578 Hom.: 0

Bravo AF: 0.00915

ESP6500AA AF: 0.0256 AC: 113

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00227 AC: 276

Asia WGS AF: 0.000867 AC: 3 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.52
DEOGEN2	Benign	0.023	T;T;T;T;.;.;T;.;T;T;T;T;.;T;T;T;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.46	N
LIST_S2	Uncertain	0.92	D;.;D;D;D;D;D;D;D;D;D;.;D;D;D;D;D
MetaRNN	Benign	0.0059	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	.;M;.;.;.;.;.;.;.;.;.;.;M;.;.;.;M
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.2	N;N;N;N;D;D;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.047
Sift	Benign	0.35	T;T;T;T;D;D;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.27	T;T;T;T;D;D;T;T;T;T;T;T;T;T;D;T;T
Polyphen		0.013	B;B;B;.;.;.;.;.;.;.;.;B;.;.;.;.;B
Vest4		0.25
MutPred		0.12		Loss of catalytic residue at V10 (P = 0.0897);Loss of catalytic residue at V10 (P = 0.0897);Loss of catalytic residue at V10 (P = 0.0897);Loss of catalytic residue at V10 (P = 0.0897);Loss of catalytic residue at V10 (P = 0.0897);Loss of catalytic residue at V10 (P = 0.0897);Loss of catalytic residue at V10 (P = 0.0897);Loss of catalytic residue at V10 (P = 0.0897);Loss of catalytic residue at V10 (P = 0.0897);Loss of catalytic residue at V10 (P = 0.0897);Loss of catalytic residue at V10 (P = 0.0897);Loss of catalytic residue at V10 (P = 0.0897);Loss of catalytic residue at V10 (P = 0.0897);Loss of catalytic residue at V10 (P = 0.0897);Loss of catalytic residue at V10 (P = 0.0897);.;Loss of catalytic residue at V10 (P = 0.0897);
MVP		0.37
MPC		0.042
ClinPred		0.0031	T
GERP RS		2.1
Varity_R		0.080
gMVP		0.33

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: rs61738593; hg19: chr6-109466452;