NM_001042475.3:c.409A>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001042475.3(CEP85L):​c.409A>G​(p.Ser137Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,613,772 control chromosomes in the GnomAD database, including 219,199 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (20040 hom., cov: 31)
  • Exomes 𝑓: 0.52 (199159 hom.)
• Consequence: CEP85L NM_001042475.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.8026297E-5).
• BP6: Variant 6-118566140-T-C is Benign according to our data. Variant chr6-118566140-T-C is described in ClinVar as Benign. ClinVar VariationId is 1209727.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

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>G	p.Ser137Gly	missense	Exon 3 of 13	NP_001035940.1	Q5SZL2-1
	CEP85L	NM_001178035.2		c.418A>G	p.Ser140Gly	missense	Exon 4 of 14	NP_001171506.1	Q5SZL2-4
	CEP85L	NM_206921.3		c.409A>G	p.Ser137Gly	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>G	p.Ser137Gly	missense	Exon 3 of 13	ENSP00000357477.3	Q5SZL2-1
	CEP85L	ENST00000434604.5	TSL:1	c.418A>G	p.Ser140Gly	missense	Exon 4 of 9	ENSP00000392131.1	A2A3P3
	CEP85L	ENST00000392500.7	TSL:1	c.418A>G	p.Ser140Gly	missense	Exon 5 of 8	ENSP00000376288.3	Q5SZL2-2

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77067 AN: 151844 Hom.: 20031 Cov.: 31

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.469

GnomAD2 exomes AF: 0.467 AC: 117525 AN: 251412 AF XY: 0.477

Gnomad AFR exome AF: 0.554

Gnomad AMR exome AF: 0.223

Gnomad ASJ exome AF: 0.445

Gnomad EAS exome AF: 0.281

Gnomad FIN exome AF: 0.525

Gnomad NFE exome AF: 0.542

Gnomad OTH exome AF: 0.496

GnomAD4 exome AF: 0.516 AC: 754629 AN: 1461810 Hom.: 199159 Cov.: 54 AF XY: 0.516 AC XY: 375300 AN XY: 727212

African (AFR) AF: 0.545 AC: 18242 AN: 33480

American (AMR) AF: 0.238 AC: 10662 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 11617 AN: 26136

East Asian (EAS) AF: 0.257 AC: 10202 AN: 39698

South Asian (SAS) AF: 0.491 AC: 42359 AN: 86258

European-Finnish (FIN) AF: 0.528 AC: 28228 AN: 53418

Middle Eastern (MID) AF: 0.510 AC: 2941 AN: 5768

European-Non Finnish (NFE) AF: 0.539 AC: 599856 AN: 1111938

Other (OTH) AF: 0.505 AC: 30522 AN: 60392

GnomAD4 genome AF: 0.507 AC: 77106 AN: 151962 Hom.: 20040 Cov.: 31 AF XY: 0.500 AC XY: 37096 AN XY: 74260

African (AFR) AF: 0.553 AC: 22917 AN: 41440

American (AMR) AF: 0.334 AC: 5101 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1547 AN: 3466

East Asian (EAS) AF: 0.282 AC: 1453 AN: 5146

South Asian (SAS) AF: 0.485 AC: 2336 AN: 4814

European-Finnish (FIN) AF: 0.522 AC: 5505 AN: 10556

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36714 AN: 67960

Other (OTH) AF: 0.469 AC: 990 AN: 2112

Alfa AF: 0.515 Hom.: 52163

Bravo AF: 0.492

TwinsUK AF: 0.534 AC: 1981

ALSPAC AF: 0.557 AC: 2146

ESP6500AA AF: 0.552 AC: 2432

ESP6500EA AF: 0.527 AC: 4529

ExAC AF: 0.485 AC: 58930

Asia WGS AF: 0.377 AC: 1311 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Lissencephaly 10 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.3
DANN	Benign	0.63
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.000048	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.11
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.012
Sift	Benign	0.59	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.049
MPC		0.071
ClinPred		0.0063	T
GERP RS		-2.6
Varity_R		0.041
gMVP		0.091
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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; COSMIC: COSV63821410;