6-109153833-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001271852.3(CEP57L1):​c.463G>T​(p.Ala155Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,445,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: CEP57L1 NM_001271852.3 missense, splice_region
• Scores: Splicing: ADA: 0.8776
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22115394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP57L1	NM_001271852.3	c.463G>T	p.Ala155Ser	missense_variant, splice_region_variant	Exon 5 of 11	ENST00000517392.6	NP_001258781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP57L1	ENST00000517392.6	c.463G>T	p.Ala155Ser	missense_variant, splice_region_variant	Exon 5 of 11	2	NM_001271852.3	ENSP00000427844.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000346 AC: 5 AN: 1445260 Hom.: 0 Cov.: 27 AF XY: 0.00000278 AC XY: 2 AN XY: 719828

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000455

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T;T;T;T;T;.;T;.;T;.;.;.;T;T;T;T
Eigen	Benign	0.080
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.82	T;.;T;D;T;T;D;T;.;D;D;T;D;T;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.22	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.90	.;L;.;.;.;.;.;.;.;L;.;.;.;.;.;L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.9	N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.055
Sift	Benign	0.064	T;T;T;T;T;T;T;T;T;D;T;T;T;T;T;T
Sift4G	Uncertain	0.047	D;T;T;T;T;T;T;D;T;T;D;D;T;T;T;T
Polyphen		0.44	B;P;P;.;.;.;.;.;P;.;.;.;.;.;.;P
Vest4		0.42
MutPred		0.39		.;Gain of phosphorylation at A155 (P = 0.0951);Gain of phosphorylation at A155 (P = 0.0951);Gain of phosphorylation at A155 (P = 0.0951);Gain of phosphorylation at A155 (P = 0.0951);Gain of phosphorylation at A155 (P = 0.0951);Gain of phosphorylation at A155 (P = 0.0951);.;Gain of phosphorylation at A155 (P = 0.0951);Gain of phosphorylation at A155 (P = 0.0951);.;.;Gain of phosphorylation at A155 (P = 0.0951);.;.;Gain of phosphorylation at A155 (P = 0.0951);
MVP		0.71
MPC		0.22
ClinPred		0.48	T
GERP RS		2.6
Varity_R		0.079
gMVP		0.050

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.88
dbscSNV1_RF	Pathogenic	0.75
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-109475036;