NM_001042475.3:c.409A>T

Variant names:

• chr6-118566140-T-A
• rs3734381
• NM_001042475.3:c.409A>T

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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 Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CEP85L NM_001042475.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 35 publications found

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]

CEP85L Gene-Disease associations (from GenCC):

• lissencephaly 10

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• lissencephaly due to LIS1 mutation

  Inheritance: AD Classification: STRONG Submitted by: Illumina

ENSG00000286339 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042475.3. 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
	CEP85L	NM_001042475.3	MANE Select	c.409A>T	p.Ser137Cys	missense	Exon 3 of 13	NP_001035940.1	Q5SZL2-1
	CEP85L	NM_001178035.2		c.418A>T	p.Ser140Cys	missense	Exon 4 of 14	NP_001171506.1	Q5SZL2-4
	CEP85L	NM_206921.3		c.409A>T	p.Ser137Cys	missense	Exon 3 of 6	NP_996804.2	Q5SZL2-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP85L	ENST00000368491.8	TSL:1 MANE Select	c.409A>T	p.Ser137Cys	missense	Exon 3 of 13	ENSP00000357477.3	Q5SZL2-1
	CEP85L	ENST00000434604.5	TSL:1	c.418A>T	p.Ser140Cys	missense	Exon 4 of 9	ENSP00000392131.1	A2A3P3
	CEP85L	ENST00000392500.7	TSL:1	c.418A>T	p.Ser140Cys	missense	Exon 5 of 8	ENSP00000376288.3	Q5SZL2-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.11
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.048
Sift	Benign	0.039	D
Sift4G	Benign	0.064	T
Polyphen		0.0010	B
Vest4		0.18
MutPred		0.15		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
Mutation Taster		=100/0	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: rs3734381; hg19: chr6-118887303;