chr6-109155294-A-G

Variant names:

• chr6-109155294-A-G
• rs143748684
• NM_001271852.3:c.644A>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001271852.3(CEP57L1):​c.644A>G​(p.Asp215Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000816 in 1,580,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000080 (0 hom.)
• Consequence: CEP57L1 NM_001271852.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00
• Publications: 1 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30856943).

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.644A>G	p.Asp215Gly	missense	Exon 6 of 11	NP_001258781.1	Q8IYX8-1
	CEP57L1	NM_001350654.2		c.644A>G	p.Asp215Gly	missense	Exon 6 of 11	NP_001337583.1
	CEP57L1	NM_001350655.2		c.644A>G	p.Asp215Gly	missense	Exon 7 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.644A>G	p.Asp215Gly	missense	Exon 6 of 11	ENSP00000427844.1	Q8IYX8-1
	CEP57L1	ENST00000359793.7	TSL:1	c.644A>G	p.Asp215Gly	missense	Exon 6 of 11	ENSP00000352841.3	Q8IYX8-1
	CEP57L1	ENST00000368970.6	TSL:5	c.644A>G	p.Asp215Gly	missense	Exon 6 of 11	ENSP00000357966.2	E5RFY4

Frequencies

GnomAD3 genomes AF: 0.0000987 AC: 15 AN: 152038 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000971 AC: 23 AN: 236938 AF XY: 0.0000621

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000326

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000201

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000798 AC: 114 AN: 1428224 Hom.: 0 Cov.: 24 AF XY: 0.0000760 AC XY: 54 AN XY: 710752

African (AFR) AF: 0.00 AC: 0 AN: 32224

American (AMR) AF: 0.0000238 AC: 1 AN: 41960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25582

East Asian (EAS) AF: 0.00 AC: 0 AN: 38600

South Asian (SAS) AF: 0.00 AC: 0 AN: 80992

European-Finnish (FIN) AF: 0.0000755 AC: 4 AN: 52996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.0000981 AC: 107 AN: 1091118

Other (OTH) AF: 0.0000339 AC: 2 AN: 59070

GnomAD4 genome AF: 0.0000987 AC: 15 AN: 152038 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74272

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

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

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

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

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 67880

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000281 Hom.: 0

Bravo AF: 0.000147

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000467 AC: 4

ExAC AF: 0.0000907 AC: 11

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	0.29
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.14
Sift	Benign	0.065	T
Sift4G	Benign	0.13	T
Polyphen		0.83	P
Vest4		0.34
MVP		0.68
MPC		0.33
ClinPred		0.46	T
GERP RS		5.0
PromoterAI		-0.0064	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.44
gMVP		0.30
Mutation Taster		=88/12	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: rs143748684; hg19: chr6-109476497;