NM_022769.5:c.51G>C

Variant names:

• chr15-90530122-G-C
• rs773241141
• NM_022769.5:c.51G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022769.5(CRTC3):​c.51G>C​(p.Glu17Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000762 in 1,311,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: CRTC3 NM_022769.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.10
• Publications: 1 publications found

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]

ACMG classification

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=0.24821979).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022769.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTC3	NM_022769.5	MANE Select	c.51G>C	p.Glu17Asp	missense	Exon 1 of 15	NP_073606.3	Q6UUV7-1
	CRTC3	NM_001042574.3		c.51G>C	p.Glu17Asp	missense	Exon 1 of 15	NP_001036039.1	Q6UUV7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTC3	ENST00000268184.11	TSL:1 MANE Select	c.51G>C	p.Glu17Asp	missense	Exon 1 of 15	ENSP00000268184.6	Q6UUV7-1
	CRTC3	ENST00000420329.6	TSL:2	c.51G>C	p.Glu17Asp	missense	Exon 1 of 15	ENSP00000416573.2	Q6UUV7-3
	CRTC3	ENST00000560098.5	TSL:1	c.51G>C	p.Glu17Asp	missense	Exon 1 of 3	ENSP00000452640.1	H0YK33

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000125 AC: 2 AN: 159376 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.62e-7 AC: 1 AN: 1311972 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 650458

African (AFR) AF: 0.00 AC: 0 AN: 26278

American (AMR) AF: 0.00 AC: 0 AN: 34764

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21064

East Asian (EAS) AF: 0.00 AC: 0 AN: 28314

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43002

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1024834

Other (OTH) AF: 0.00 AC: 0 AN: 51236

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000170 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.41	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.1
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.29
Sift	Benign	0.036	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.10		Loss of ubiquitination at K18 (P = 0.0561)
MVP		0.46
MPC		2.0
ClinPred		0.86	D
GERP RS		2.5
PromoterAI		0.0044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.47
Mutation Taster		=55/45	polymorphism

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

Other links and lift over

dbSNP: rs773241141; hg19: chr15-91073354;