Genetic Variant NM_000078.3:c.85G>C (chr16-56962064-G-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_000078.3(CETP):c.85G>C(p.Val29Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CETP
NM_000078.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.41

Variant links:

Genes affected

CETP (HGNC:1869): (cholesteryl ester transfer protein) The protein encoded by this gene is found in plasma, where it is involved in the transfer of cholesteryl ester from high density lipoprotein (HDL) to other lipoproteins. Defects in this gene are a cause of hyperalphalipoproteinemia 1 (HALP1). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

CETP links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.819

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3 link	c.85G>C	p.Val29Leu	missense_variant	Exon 1 of 16	ENST00000200676.8	NP_000069.2	P11597-1A0A0S2Z3F6
CETP	NM_001286085.2 link	c.85G>C	p.Val29Leu	missense_variant	Exon 1 of 15		NP_001273014.1	A0A0S2Z3I8B4DMZ5
CETP	XM_006721124.4 link	c.85G>C	p.Val29Leu	missense_variant	Exon 1 of 9		XP_006721187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CETP	ENST00000200676.8 link	c.85G>C	p.Val29Leu	missense_variant	Exon 1 of 16	1	NM_000078.3	ENSP00000200676.3	P11597-1
CETP	ENST00000379780.6 link	c.85G>C	p.Val29Leu	missense_variant	Exon 1 of 15	1		ENSP00000369106.2	P11597-2
CETP	ENST00000569082.1 link	n.83G>C		non_coding_transcript_exon_variant	Exon 1 of 9	5
CETP	ENST00000566128.1 link	c.-310G>C		upstream_gene_variant		5		ENSP00000456276.1	H3BRJ9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250984

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135704

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461750

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

T;.

Eigen

Benign

0.017

Eigen_PC

Benign

-0.088

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.055

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Benign

0.43

PROVEAN

Benign

-2.0

N;D

REVEL

Benign

0.21

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.99

D;D

Vest4

0.56

MutPred

0.76

Loss of ubiquitination at K34 (P = 0.2258);Loss of ubiquitination at K34 (P = 0.2258);

MVP

0.48

MPC

0.53

ClinPred

0.95

GERP RS

3.1

Varity_R

0.69

gMVP

0.58

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over