11-788276-C-T

Variant names:

• chr11-788276-C-T
• NM_016564.4:c.301G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016564.4(CEND1):​c.301G>A​(p.Ala101Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A101G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CEND1 NM_016564.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.44
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3507517).

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.301G>A	p.Ala101Thr	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.301G>A	p.Ala101Thr	missense	Exon 2 of 2	ENSP00000328336.4	Q8N111
	CEND1	ENST00000901135.1		c.301G>A	p.Ala101Thr	missense	Exon 2 of 2	ENSP00000571194.1
	CEND1	ENST00000901136.1		c.301G>A	p.Ala101Thr	missense	Exon 2 of 2	ENSP00000571195.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460680 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726648

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111514

Other (OTH) AF: 0.00 AC: 0 AN: 60318

GnomAD4 genome Cov.: 33

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	0.15
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D
Eigen	Benign	0.076
Eigen_PC	Benign	0.0016
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.4
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.16
Sift	Uncertain	0.010	D
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.33
MutPred		0.13		Gain of phosphorylation at A101 (P = 0.0068)
MVP		0.23
MPC		0.55
ClinPred		0.95	D
GERP RS		4.8
Varity_R		0.20
gMVP		0.16
Mutation Taster		=97/3	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

hg19: chr11-788276;