chr6-118483726-C-T

Position:

• chr6-118483726-C-T

Variant summary

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

The NM_001042475.3(CEP85L):​c.1570G>A​(p.Val524Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP85L NM_001042475.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.62

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]

LOC105377971 (HGNC:):

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=0.07681802).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP85L	NM_001042475.3	c.1570G>A	p.Val524Ile	missense_variant	7/13	ENST00000368491.8	NP_001035940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP85L	ENST00000368491.8	c.1570G>A	p.Val524Ile	missense_variant	7/13	1	NM_001042475.3	ENSP00000357477.3
CEP85L	ENST00000434604.5	c.1579G>A	p.Val527Ile	missense_variant	8/9	1		ENSP00000392131.1
CEP85L	ENST00000368488.9	c.1579G>A	p.Val527Ile	missense_variant	8/14	5		ENSP00000357474.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Jun 27, 2024

Variant summary: CEP85L c.1570G>A (p.Val524Ile) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 248808 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1570G>A in individuals affected with Lissencephaly 10 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	21
DANN	Benign	0.89
DEOGEN2	Benign	0.0023	T;.;T
Eigen	Benign	0.077
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.077	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.81	L;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.25	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.60	T;T;T
Sift4G	Benign	0.52	T;T;.
Polyphen		0.75	P;.;.
Vest4		0.079
MutPred		0.11		Gain of catalytic residue at L529 (P = 0.0275);.;.;
MVP		0.33
MPC		0.091
ClinPred		0.53	D
GERP RS		4.9
Varity_R		0.057
gMVP		0.090

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs779031422; hg19: chr6-118804889;