rs149620345

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-788486-C-G
• chr11-788486-C-T

Variant summary

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

The NM_016564.4(CEND1):​c.91G>C​(p.Asp31His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,390,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. D31N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CEND1 NM_016564.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.52
• 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=0.35584086).

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>C	p.Asp31His	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>C	p.Asp31His	missense	Exon 2 of 2	ENSP00000328336.4	Q8N111
	CEND1	ENST00000901135.1		c.91G>C	p.Asp31His	missense	Exon 2 of 2	ENSP00000571194.1
	CEND1	ENST00000901136.1		c.91G>C	p.Asp31His	missense	Exon 2 of 2	ENSP00000571195.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1390752 Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1 AN XY: 685014

African (AFR) AF: 0.00 AC: 0 AN: 30856

American (AMR) AF: 0.00 AC: 0 AN: 33640

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

East Asian (EAS) AF: 0.00 AC: 0 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: 9.29e-7 AC: 1 AN: 1076052

Other (OTH) AF: 0.00 AC: 0 AN: 57062

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	0.0035	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D
Eigen	Benign	0.12
Eigen_PC	Benign	-0.0086
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.15
Sift	Uncertain	0.012	D
Sift4G	Benign	0.096	T
Polyphen		1.0	D
Vest4		0.23
MutPred		0.18		Loss of ubiquitination at K33 (P = 0.0311)
MVP		0.38
MPC		0.67
ClinPred		0.95	D
GERP RS		3.6
Varity_R		0.16
gMVP		0.34
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;