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15-90530197-G-A

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

2

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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.475 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CRTC3NM_022769.5 linkuse as main transcriptc.126G>A p.Leu42= synonymous_variant 1/15 ENST00000268184.11
CRTC3NM_001042574.3 linkuse as main transcriptc.126G>A p.Leu42= synonymous_variant 1/15

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CRTC3ENST00000268184.11 linkuse as main transcriptc.126G>A p.Leu42= synonymous_variant 1/151 NM_022769.5 P3Q6UUV7-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000358
AC:
53
AN:
147966
Hom.:
0
Cov.:
31
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:
47
AN:
77182
Hom.:
0
AF XY:
0.000675
AC XY:
30
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.:
1
Cov.:
30
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000358
AC:
53
AN:
148070
Hom.:
0
Cov.:
31
AF XY:
0.000277
AC XY:
20
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.:
0
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 submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2023CRTC3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
Cadd
Benign
13
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.

Other links and lift over

dbSNP: rs188476026; hg19: chr15-91073429; API