Genetic Variant CNEP1R1:p.Ala12Thr (chr16-50026404-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001281789.2(CNEP1R1):c.34G>A(p.Ala12Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000825 in 1,455,058 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

CNEP1R1
NM_001281789.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.87

Publications

0 publications found

Variant links:

Genes affected

CNEP1R1 (HGNC:26759): (CTD nuclear envelope phosphatase 1 regulatory subunit 1) This gene encodes a transmembrane protein that belongs to the Tmemb_18A family. A similar protein in yeast is a component of an endoplasmic reticulum-associated protein phosphatase complex and is thought to play a role in the synthesis of triacylglycerol. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

CNEP1R1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001281789.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNEP1R1	NM_001281789.2	MANE Select	c.34G>A	p.Ala12Thr	missense	Exon 2 of 6	NP_001268718.1	Q8N9A8-1
CNEP1R1	NM_153261.6		c.85G>A	p.Ala29Thr	missense	Exon 3 of 7	NP_694993.2
CNEP1R1	NR_104042.2		n.176G>A		non_coding_transcript_exon	Exon 3 of 6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNEP1R1	ENST00000427478.7	TSL:1 MANE Select	c.34G>A	p.Ala12Thr	missense	Exon 2 of 6	ENSP00000394224.2	Q8N9A8-1
CNEP1R1	ENST00000458059.7	TSL:1	c.85G>A	p.Ala29Thr	missense	Exon 3 of 7	ENSP00000405635.3	Q8N9A8-2
CNEP1R1	ENST00000565556.5	TSL:1	c.-63G>A		5_prime_UTR	Exon 2 of 6	ENSP00000457787.1	H3BUT5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000415

AC:

AN:

240922

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000919

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000825

AC:

AN:

1455058

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

723310

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33410

American (AMR)

AF:

0.00

AC:

AN:

44032

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25956

East Asian (EAS)

AF:

0.00

AC:

AN:

39614

South Asian (SAS)

AF:

0.00

AC:

AN:

84976

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53136

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1108076

Other (OTH)

AF:

0.00

AC:

AN:

60126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.38

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.56

MetaSVM

Uncertain

-0.11

MutationAssessor

Uncertain

2.4

PhyloP100

8.9

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.50

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.69

MutPred

0.63

Gain of phosphorylation at A12 (P = 0.0205)

MVP

0.35

MPC

2.2

ClinPred

0.94

GERP RS

5.6

PromoterAI

-0.0049

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.45

gMVP

0.95

Mutation Taster

=25/75

disease causing

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over