Variant 15-90530197-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_022769.5(CRTC3):c.126G>A(p.Leu42=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000346 in 1,268,648 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00034 ( 1 hom. )

Consequence

CRTC3
NM_022769.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.475

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 15-90530197-G-A is Benign according to our data. Variant chr15-90530197-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2645708.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.475 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRTC3	NM_022769.5 linkuse as main transcript	c.126G>A	p.Leu42=	synonymous_variant	1/15	ENST00000268184.11
CRTC3	NM_001042574.3 linkuse as main transcript	c.126G>A	p.Leu42=	synonymous_variant	1/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRTC3	ENST00000268184.11 linkuse as main transcript	c.126G>A	p.Leu42=	synonymous_variant	1/15	1	NM_022769.5	P3	Q6UUV7-1

Frequencies

GnomAD3 genomes

AF:

0.000358

AC:

AN:

147966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000489

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000805

Gnomad ASJ

AF:

0.000874

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000836

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00645

Gnomad NFE

AF:

0.000449

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000609

AC:

AN:

77182

Hom.:

AF XY:

0.000675

AC XY:

AN XY:

44418

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00143

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000790

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000503

Gnomad OTH exome

AF:

0.00145

GnomAD4 exome

AF:

0.000344

AC:

386

AN:

1120578

Hom.:

Cov.:

AF XY:

0.000380

AC XY:

208

AN XY:

547802

show subpopulations

Gnomad4 AFR exome

AF:

0.0000901

Gnomad4 AMR exome

AF:

0.000453

Gnomad4 ASJ exome

AF:

0.00128

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000297

Gnomad4 OTH exome

AF:

0.000511

GnomAD4 genome

AF:

0.000358

AC:

AN:

148070

Hom.:

Cov.:

AF XY:

0.000277

AC XY:

AN XY:

72160

show subpopulations

Gnomad4 AFR

AF:

0.0000488

Gnomad4 AMR

AF:

0.000804

Gnomad4 ASJ

AF:

0.000874

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000837

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000449

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000783

Hom.:

Bravo

AF:

0.000370

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

CRTC3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.97

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over