Genetic Variant CRTC3:p.Val390Leu (chr15-90629434-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022769.5(CRTC3):c.1168G>C(p.Val390Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CRTC3
NM_022769.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.32

Variant links:

Genes affected

CRTC3 (HGNC:26148): (CREB regulated transcription coactivator 3) This gene is a member of the CREB regulated transcription coactivator gene family. This family regulates CREB-dependent gene transcription in a phosphorylation-independent manner and may be selective for cAMP-responsive genes. The protein encoded by this gene may induce mitochondrial biogenesis and attenuate catecholamine signaling in adipose tissue. A translocation event between this gene and Notch coactivator mastermind-like gene 2, which results in a fusion protein, has been reported in mucoepidermoid carcinomas. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

CRTC3 links:

CRTC3-AS1 (HGNC:51433): (CRTC3 antisense RNA 1)

CRTC3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21572849).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC3	NM_022769.5 link	c.1168G>C	p.Val390Leu	missense_variant	Exon 11 of 15	ENST00000268184.11	NP_073606.3	Q6UUV7-1Q8TEF4
CRTC3	NM_001042574.3 link	c.1168G>C	p.Val390Leu	missense_variant	Exon 11 of 15		NP_001036039.1	Q6UUV7-3Q8TEF4
CRTC3-AS1	NR_120372.1 link	n.510-9281C>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CRTC3	ENST00000268184.11 link	c.1168G>C	p.Val390Leu	missense_variant	Exon 11 of 15	1	NM_022769.5	ENSP00000268184.6	Q6UUV7-1
CRTC3	ENST00000420329.6 link	c.1168G>C	p.Val390Leu	missense_variant	Exon 11 of 15	2		ENSP00000416573.2	Q6UUV7-3
CRTC3	ENST00000686240.1 link	n.*581G>C		non_coding_transcript_exon_variant	Exon 10 of 14			ENSP00000508866.1	A0A8I5KTH9
CRTC3	ENST00000691029.1 link	n.1168G>C		non_coding_transcript_exon_variant	Exon 11 of 17			ENSP00000510507.1	Q6UUV7-1
CRTC3	ENST00000692149.1 link	n.*495G>C		non_coding_transcript_exon_variant	Exon 9 of 13			ENSP00000510448.1	A0A8I5KTH9
CRTC3	ENST00000686240.1 link	n.*581G>C		3_prime_UTR_variant	Exon 10 of 14			ENSP00000508866.1	A0A8I5KTH9
CRTC3	ENST00000692149.1 link	n.*495G>C		3_prime_UTR_variant	Exon 9 of 13			ENSP00000510448.1	A0A8I5KTH9
CRTC3	ENST00000687075.1 link	n.*404G>C		downstream_gene_variant				ENSP00000510590.1	A0A8I5QJV4

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151910

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727234

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

AF:

0.0000132

AC:

AN:

151910

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74186

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.078

.;T

Eigen

Benign

-0.0076

Eigen_PC

Benign

-0.0075

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.0082

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.55

N;N

REVEL

Benign

0.13

Sift

Benign

0.62

T;T

Sift4G

Benign

0.85

T;T

Polyphen

0.97

D;P

Vest4

0.31

MutPred

0.23

Gain of glycosylation at P392 (P = 0.0898);Gain of glycosylation at P392 (P = 0.0898);

MVP

0.22

MPC

0.13

ClinPred

0.45

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.019

gMVP

0.33

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