chr6-109145249-G-T

Variant names:

• chr6-109145249-G-T
• rs61738593
• NM_001271852.3:c.28G>T

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V10A) has been classified as Uncertain significance.

• 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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP57L1	NM_001271852.3	MANE Select	c.28G>T	p.Val10Leu	missense	Exon 2 of 11	NP_001258781.1	Q8IYX8-1
	CEP57L1	NM_001350654.2		c.28G>T	p.Val10Leu	missense	Exon 2 of 11	NP_001337583.1
	CEP57L1	NM_001350655.2		c.28G>T	p.Val10Leu	missense	Exon 3 of 12	NP_001337584.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP57L1	ENST00000517392.6	TSL:2 MANE Select	c.28G>T	p.Val10Leu	missense	Exon 2 of 11	ENSP00000427844.1	Q8IYX8-1
	CEP57L1	ENST00000359793.7	TSL:1	c.28G>T	p.Val10Leu	missense	Exon 2 of 11	ENSP00000352841.3	Q8IYX8-1
	CEP57L1	ENST00000368970.6	TSL:5	c.28G>T	p.Val10Leu	missense	Exon 2 of 11	ENSP00000357966.2	E5RFY4

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

GnomAD2 exomes AF: 0.00183 AC: 454 AN: 247880 AF XY: 0.00134

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 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

African (AFR) AF: 0.0276 AC: 906 AN: 32852

American (AMR) AF: 0.000944 AC: 42 AN: 44482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25820

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39498

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85324

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53240

Middle Eastern (MID) AF: 0.000398 AC: 2 AN: 5024

European-Non Finnish (NFE) AF: 0.0000109 AC: 12 AN: 1096038

Other (OTH) AF: 0.00148 AC: 88 AN: 59562

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

African (AFR) AF: 0.0256 AC: 1064 AN: 41486

American (AMR) AF: 0.00368 AC: 56 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67822

Other (OTH) AF: 0.00617 AC: 13 AN: 2106

Alfa AF: 0.00229 Hom.: 7

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.46	N
LIST_S2	Uncertain	0.92	D
MetaRNN	Benign	0.0059	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.91
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.047
Sift	Benign	0.35	T
Sift4G	Benign	0.27	T
Polyphen		0.013	B
Vest4		0.25
MutPred		0.12		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
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs61738593; hg19: chr6-109466452;