rs534287635

Variant names:

• chr15-90638606-C-A
• rs534287635
• NM_022769.5:c.1427C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-90638606-C-A
• chr15-90638606-C-T

Variant summary

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

The NM_022769.5(CRTC3):​c.1427C>A​(p.Ser476Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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: not found (cov: 31)
• Consequence: CRTC3 NM_022769.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67

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=0.29329044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC3	NM_022769.5	c.1427C>A	p.Ser476Tyr	missense_variant	Exon 12 of 15	ENST00000268184.11	NP_073606.3
CRTC3	NM_001042574.3	c.1427C>A	p.Ser476Tyr	missense_variant	Exon 12 of 15		NP_001036039.1
CRTC3-AS1	NR_120372.1	n.509+2436G>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTC3	ENST00000268184.11	c.1427C>A	p.Ser476Tyr	missense_variant	Exon 12 of 15	1	NM_022769.5	ENSP00000268184.6
CRTC3	ENST00000420329.6	c.1427C>A	p.Ser476Tyr	missense_variant	Exon 12 of 15	2		ENSP00000416573.2
CRTC3	ENST00000686240.1	n.*840C>A		non_coding_transcript_exon_variant	Exon 11 of 14			ENSP00000508866.1
CRTC3	ENST00000691029.1	n.1427C>A		non_coding_transcript_exon_variant	Exon 12 of 17			ENSP00000510507.1
CRTC3	ENST00000692149.1	n.*754C>A		non_coding_transcript_exon_variant	Exon 10 of 13			ENSP00000510448.1
CRTC3	ENST00000686240.1	n.*840C>A		3_prime_UTR_variant	Exon 11 of 14			ENSP00000508866.1
CRTC3	ENST00000692149.1	n.*754C>A		3_prime_UTR_variant	Exon 10 of 13			ENSP00000510448.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.58
DEOGEN2	Benign	0.17	.;T
Eigen	Benign	0.031
Eigen_PC	Benign	-0.0030
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.16
Sift	Benign	0.81	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.76	P;P
Vest4		0.48
MutPred		0.40		Gain of catalytic residue at S476 (P = 0.0028);Gain of catalytic residue at S476 (P = 0.0028);
MVP		0.19
MPC		0.20
ClinPred		0.47	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.41

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: rs534287635; hg19: chr15-91181838;