11-788486-C-T

Variant names:

• chr11-788486-C-T
• rs149620345
• NM_016564.4:c.91G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016564.4(CEND1):​c.91G>A​(p.Asp31Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000395 in 1,542,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: CEND1 NM_016564.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.52
• Publications: 2 publications found

Genes affected

CEND1 (HGNC:24153): (cell cycle exit and neuronal differentiation 1) The protein encoded by this gene is a neuron-specific protein. The similar protein in pig enhances neuroblastoma cell differentiation in vitro and may be involved in neuronal differentiation in vivo. Multiple pseudogenes have been reported for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19505003).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016564.4. 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
	CEND1	NM_016564.4	MANE Select	c.91G>A	p.Asp31Asn	missense	Exon 2 of 2	NP_057648.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEND1	ENST00000330106.5	TSL:1 MANE Select	c.91G>A	p.Asp31Asn	missense	Exon 2 of 2	ENSP00000328336.4	Q8N111
	CEND1	ENST00000901135.1		c.91G>A	p.Asp31Asn	missense	Exon 2 of 2	ENSP00000571194.1
	CEND1	ENST00000901136.1		c.91G>A	p.Asp31Asn	missense	Exon 2 of 2	ENSP00000571195.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152118 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000408 AC: 8 AN: 196030 AF XY: 0.0000283

Gnomad AFR exome AF: 0.000272

Gnomad AMR exome AF: 0.0000830

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000617

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000109

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000395 AC: 55 AN: 1390752 Hom.: 0 Cov.: 31 AF XY: 0.0000365 AC XY: 25 AN XY: 685014

African (AFR) AF: 0.000130 AC: 4 AN: 30856

American (AMR) AF: 0.0000595 AC: 2 AN: 33640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21944

East Asian (EAS) AF: 0.0000514 AC: 2 AN: 38882

South Asian (SAS) AF: 0.00 AC: 0 AN: 77564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4570

European-Non Finnish (NFE) AF: 0.0000427 AC: 46 AN: 1076052

Other (OTH) AF: 0.0000175 AC: 1 AN: 57062

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152236 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74426

African (AFR) AF: 0.000144 AC: 6 AN: 41562

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67978

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000670 Hom.: 0

Bravo AF: 0.0000529

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000578 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Benign	0.051
Eigen_PC	Benign	-0.066
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.5
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.11
Sift	Benign	0.052	T
Sift4G	Benign	0.35	T
Polyphen		1.0	D
Vest4		0.21
MVP		0.41
MPC		0.56
ClinPred		0.13	T
GERP RS		3.6
Varity_R		0.076
gMVP		0.22
Mutation Taster		=95/5	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: rs149620345; hg19: chr11-788486; COSMIC: COSV57192432; COSMIC: COSV57192432;