NM_001271852.3:c.463G>A

Variant names:

• chr6-109153833-G-A
• rs372766890
• NM_001271852.3:c.463G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001271852.3(CEP57L1):​c.463G>A​(p.Ala155Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000275 in 1,597,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: CEP57L1 NM_001271852.3 missense, splice_region
• Scores: Splicing: ADA: 0.05620
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05747077).

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.463G>A	p.Ala155Thr	missense splice_region	Exon 5 of 11	NP_001258781.1	Q8IYX8-1
	CEP57L1	NM_001350654.2		c.463G>A	p.Ala155Thr	missense splice_region	Exon 5 of 11	NP_001337583.1
	CEP57L1	NM_001350655.2		c.463G>A	p.Ala155Thr	missense splice_region	Exon 6 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.463G>A	p.Ala155Thr	missense splice_region	Exon 5 of 11	ENSP00000427844.1	Q8IYX8-1
	CEP57L1	ENST00000359793.7	TSL:1	c.463G>A	p.Ala155Thr	missense splice_region	Exon 5 of 11	ENSP00000352841.3	Q8IYX8-1
	CEP57L1	ENST00000368970.6	TSL:5	c.463G>A	p.Ala155Thr	missense splice_region	Exon 5 of 11	ENSP00000357966.2	E5RFY4

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 151880 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000443 AC: 11 AN: 248292 AF XY: 0.0000298

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000899

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000889

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000270 AC: 39 AN: 1445260 Hom.: 0 Cov.: 27 AF XY: 0.0000194 AC XY: 14 AN XY: 719828

African (AFR) AF: 0.00 AC: 0 AN: 32954

American (AMR) AF: 0.00 AC: 0 AN: 43908

Ashkenazi Jewish (ASJ) AF: 0.000885 AC: 23 AN: 25978

East Asian (EAS) AF: 0.00 AC: 0 AN: 39440

South Asian (SAS) AF: 0.00 AC: 0 AN: 85202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5096

European-Non Finnish (NFE) AF: 0.0000127 AC: 14 AN: 1099580

Other (OTH) AF: 0.0000335 AC: 2 AN: 59750

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 151880 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74166

African (AFR) AF: 0.00 AC: 0 AN: 41356

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.000135 Hom.: 0

Bravo AF: 0.0000302

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.00

EpiControl AF: 0.0000594

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.033
Sift	Benign	0.28	T
Sift4G	Benign	0.35	T
Polyphen		0.0050	B
Vest4		0.23
MVP		0.70
MPC		0.072
ClinPred		0.070	T
GERP RS		2.6
Varity_R		0.070
gMVP		0.052
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.056
dbscSNV1_RF	Benign	0.28
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: rs372766890; hg19: chr6-109475036;