6-109146758-C-G

Variant names:

• chr6-109146758-C-G
• rs1234523383
• NM_001271852.3:c.161C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.161C>G	p.Ala54Gly	missense splice_region	Exon 3 of 11	NP_001258781.1	Q8IYX8-1
	CEP57L1	NM_001350654.2		c.161C>G	p.Ala54Gly	missense splice_region	Exon 3 of 11	NP_001337583.1
	CEP57L1	NM_001350655.2		c.161C>G	p.Ala54Gly	missense splice_region	Exon 4 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.161C>G	p.Ala54Gly	missense splice_region	Exon 3 of 11	ENSP00000427844.1	Q8IYX8-1
	CEP57L1	ENST00000359793.7	TSL:1	c.161C>G	p.Ala54Gly	missense splice_region	Exon 3 of 11	ENSP00000352841.3	Q8IYX8-1
	CEP57L1	ENST00000368970.6	TSL:5	c.161C>G	p.Ala54Gly	missense splice_region	Exon 3 of 11	ENSP00000357966.2	E5RFY4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000529 AC: 1 AN: 188998 AF XY: 0.00000963

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 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: 1 AN: 1398454 Hom.: 0 Cov.: 29 AF XY: 0.00000144 AC XY: 1 AN XY: 694024

African (AFR) AF: 0.00 AC: 0 AN: 29580

American (AMR) AF: 0.00 AC: 0 AN: 29872

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23492

East Asian (EAS) AF: 0.00 AC: 0 AN: 37688

South Asian (SAS) AF: 0.00 AC: 0 AN: 76136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5460

European-Non Finnish (NFE) AF: 9.20e-7 AC: 1 AN: 1086604

Other (OTH) AF: 0.00 AC: 0 AN: 57546

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

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	Uncertain	0.35
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		5.4
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.27
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.66
MutPred		0.14		Gain of catalytic residue at P50 (P = 0.0696)
MVP		0.74
MPC		0.30
ClinPred		0.94	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.46
gMVP		0.36
Mutation Taster		=48/52	disease causing

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

Other links and lift over

dbSNP: rs1234523383; hg19: chr6-109467961;