rs201378392

Variant names:

• chr15-90629324-C-A
• rs201378392
• NM_022769.5:c.1058C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-90629324-C-A
• chr15-90629324-C-G
• chr15-90629324-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022769.5(CRTC3):​c.1058C>A​(p.Ser353Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 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: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CRTC3 NM_022769.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC3	NM_022769.5	c.1058C>A	p.Ser353Tyr	missense_variant	Exon 11 of 15	ENST00000268184.11	NP_073606.3
CRTC3	NM_001042574.3	c.1058C>A	p.Ser353Tyr	missense_variant	Exon 11 of 15		NP_001036039.1
CRTC3-AS1	NR_120372.1	n.510-9171G>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTC3	ENST00000268184.11	c.1058C>A	p.Ser353Tyr	missense_variant	Exon 11 of 15	1	NM_022769.5	ENSP00000268184.6
CRTC3	ENST00000420329.6	c.1058C>A	p.Ser353Tyr	missense_variant	Exon 11 of 15	2		ENSP00000416573.2
CRTC3	ENST00000686240.1	n.*471C>A		non_coding_transcript_exon_variant	Exon 10 of 14			ENSP00000508866.1
CRTC3	ENST00000691029.1	n.1058C>A		non_coding_transcript_exon_variant	Exon 11 of 17			ENSP00000510507.1
CRTC3	ENST00000692149.1	n.*385C>A		non_coding_transcript_exon_variant	Exon 9 of 13			ENSP00000510448.1
CRTC3	ENST00000686240.1	n.*471C>A		3_prime_UTR_variant	Exon 10 of 14			ENSP00000508866.1
CRTC3	ENST00000692149.1	n.*385C>A		3_prime_UTR_variant	Exon 9 of 13			ENSP00000510448.1
CRTC3	ENST00000687075.1	n.*294C>A		downstream_gene_variant				ENSP00000510590.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461862 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	.;T
Eigen	Benign	0.11
Eigen_PC	Benign	-0.058
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.0054	T
MetaRNN	Uncertain	0.50	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.19
Sift	Uncertain	0.016	D;D
Sift4G	Benign	0.11	T;T
Polyphen		1.0	D;D
Vest4		0.56
MutPred		0.34		Gain of catalytic residue at S353 (P = 0.025);Gain of catalytic residue at S353 (P = 0.025);
MVP		0.13
MPC		0.29
ClinPred		0.87	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.095
gMVP		0.65

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: rs201378392; hg19: chr15-91172556;