dbSNP rs2066086704: CEMP1:p.Pro35Arg (chr16-2530970-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001048212.3(CEMP1):c.104C>G(p.Pro35Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,210 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CEMP1
NM_001048212.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.673

Publications

0 publications found

Variant links:

Genes affected

CEMP1 (HGNC:32553): (cementum protein 1) Enables hydroxyapatite binding activity. Involved in several processes, including biomineral tissue development; cell population proliferation; and odontogenesis. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CEMP1 links:

AMDHD2 (HGNC:24262): (amidohydrolase domain containing 2) Enables N-acetylglucosamine-6-phosphate deacetylase activity. Predicted to be involved in N-acetylglucosamine catabolic process. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

AMDHD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.174826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEMP1	NM_001048212.3 link	c.104C>G	p.Pro35Arg	missense_variant	Exon 1 of 1	ENST00000567119.1	NP_001041677.1	Q6PRD7
AMDHD2	NM_001330449.2 link	c.*1407G>C		3_prime_UTR_variant	Exon 11 of 11	ENST00000293971.11	NP_001317378.1	Q9Y303-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEMP1	ENST00000567119.1 link	c.104C>G	p.Pro35Arg	missense_variant	Exon 1 of 1	6	NM_001048212.3	ENSP00000457380.1		Q6PRD7
AMDHD2	ENST00000293971.11 link	c.*1407G>C		3_prime_UTR_variant	Exon 11 of 11	1	NM_001330449.2	ENSP00000293971.6		Q9Y303-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461210

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726896

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52914

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111912

Other (OTH)

AF:

0.00

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 06, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.104C>G (p.P35R) alteration is located in exon 1 (coding exon 1) of the CEMP1 gene. This alteration results from a C to G substitution at nucleotide position 104, causing the proline (P) at amino acid position 35 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.088

T;.

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.26

T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.

PhyloP100

0.67

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-9.0

D;D

Polyphen

1.0

D;.

Vest4

0.20

MutPred

0.085

Gain of methylation at P35 (P = 0.0199);Gain of methylation at P35 (P = 0.0199);

MVP

0.25

ClinPred

0.38

GERP RS

1.4

PromoterAI

-0.023

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.37

gMVP

0.028

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over