15-90625805-G-C

Variant names:

• chr15-90625805-G-C
• rs759844206
• NM_022769.5:c.779G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022769.5(CRTC3):​c.779G>C​(p.Gly260Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CRTC3 NM_022769.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.63

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26414192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC3	NM_022769.5	c.779G>C	p.Gly260Ala	missense_variant	Exon 10 of 15	ENST00000268184.11	NP_073606.3
CRTC3	NM_001042574.3	c.779G>C	p.Gly260Ala	missense_variant	Exon 10 of 15		NP_001036039.1
CRTC3-AS1	NR_120372.1	n.510-5652C>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTC3	ENST00000268184.11	c.779G>C	p.Gly260Ala	missense_variant	Exon 10 of 15	1	NM_022769.5	ENSP00000268184.6
CRTC3	ENST00000420329.6	c.779G>C	p.Gly260Ala	missense_variant	Exon 10 of 15	2		ENSP00000416573.2
CRTC3	ENST00000558005.1	c.434G>C	p.Gly145Ala	missense_variant	Exon 7 of 7	4		ENSP00000452676.1
CRTC3	ENST00000686240.1	n.*192G>C		non_coding_transcript_exon_variant	Exon 9 of 14			ENSP00000508866.1
CRTC3	ENST00000687075.1	n.*15G>C		non_coding_transcript_exon_variant	Exon 8 of 9			ENSP00000510590.1
CRTC3	ENST00000691029.1	n.779G>C		non_coding_transcript_exon_variant	Exon 10 of 17			ENSP00000510507.1
CRTC3	ENST00000692149.1	n.*106G>C		non_coding_transcript_exon_variant	Exon 8 of 13			ENSP00000510448.1
CRTC3	ENST00000686240.1	n.*192G>C		3_prime_UTR_variant	Exon 9 of 14			ENSP00000508866.1
CRTC3	ENST00000687075.1	n.*15G>C		3_prime_UTR_variant	Exon 8 of 9			ENSP00000510590.1
CRTC3	ENST00000692149.1	n.*106G>C		3_prime_UTR_variant	Exon 8 of 13			ENSP00000510448.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000403 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	.;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.065
Sift	Benign	0.15	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.51	P;P
Vest4		0.37
MutPred		0.27		Loss of disorder (P = 0.083);Loss of disorder (P = 0.083);
MVP		0.12
MPC		0.077
ClinPred		0.79	D
GERP RS		5.4
Varity_R		0.12
gMVP		0.43

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

Other links and lift over

dbSNP: rs759844206; hg19: chr15-91169037;