rs3734381

Positions:

• chr6-118566140-T-A
• chr6-118566140-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001042475.3(CEP85L):​c.409A>T​(p.Ser137Cys) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S137G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CEP85L NM_001042475.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05791071).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP85L	NM_001042475.3	c.409A>T	p.Ser137Cys	missense_variant	3/13	ENST00000368491.8	NP_001035940.1
LOC107986524	XR_007059725.1	n.90+370T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP85L	ENST00000368491.8	c.409A>T	p.Ser137Cys	missense_variant	3/13	1	NM_001042475.3	ENSP00000357477	P1
	ENST00000659521.1	n.111+370T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.0071	T;.;T;.;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.50	T;T;T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.058	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;.;.;.;.;L
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N
REVEL	Benign	0.048
Sift	Benign	0.039	D;D;D;D;D;D
Sift4G	Benign	0.064	T;T;.;T;T;T
Polyphen		0.0010	B;.;.;.;B;.
Vest4		0.18
MutPred		0.15		Loss of phosphorylation at S137 (P = 0.0287);.;.;.;.;Loss of phosphorylation at S137 (P = 0.0287);
MVP		0.081
MPC		0.30
ClinPred		0.075	T
GERP RS		-2.6
Varity_R		0.054
gMVP		0.13

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

Publications

LitVar

Other links and lift over

dbSNP: rs3734381; hg19: chr6-118887303;