6-118481816-T-C
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001042475.3(CEP85L):c.1708A>G(p.Lys570Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,594,296 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 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
CEP85L
NM_001042475.3 missense
NM_001042475.3 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 3.34
Genes affected
CEP85L (HGNC:21638): (centrosomal protein 85 like) The protein encoded by this gene was identified as a breast cancer antigen. Nothing more is known of its function at this time. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.12878883).
BS2
?
High AC in GnomAd at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP85L | NM_001042475.3 | c.1708A>G | p.Lys570Glu | missense_variant | 8/13 | ENST00000368491.8 | |
LOC105377971 | XR_001743824.3 | n.139-294T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP85L | ENST00000368491.8 | c.1708A>G | p.Lys570Glu | missense_variant | 8/13 | 1 | NM_001042475.3 | P1 | |
CEP85L | ENST00000434604.5 | c.1717A>G | p.Lys573Glu | missense_variant | 9/9 | 1 | |||
CEP85L | ENST00000368488.9 | c.1717A>G | p.Lys573Glu | missense_variant | 9/14 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152112Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000172 AC: 4AN: 232692Hom.: 0 AF XY: 0.00000792 AC XY: 1AN XY: 126278
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 13, 2021 | The c.1708A>G (p.K570E) alteration is located in exon 8 (coding exon 8) of the CEP85L gene. This alteration results from a A to G substitution at nucleotide position 1708, causing the lysine (K) at amino acid position 570 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;.
Polyphen
P;.;.
Vest4
MutPred
Loss of methylation at K570 (P = 0.0036);.;.;
MVP
MPC
0.15
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at