rs201346508

Variant names:

• chr15-90638768-G-A
• rs201346508
• NM_022769.5:c.1501G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-90638768-G-A
• chr15-90638768-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022769.5(CRTC3):​c.1501G>A​(p.Gly501Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CRTC3 NM_022769.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.926

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051576793).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC3	NM_022769.5	c.1501G>A	p.Gly501Ser	missense_variant	Exon 13 of 15	ENST00000268184.11	NP_073606.3
CRTC3	NM_001042574.3	c.1501G>A	p.Gly501Ser	missense_variant	Exon 13 of 15		NP_001036039.1
CRTC3-AS1	NR_120372.1	n.509+2274C>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTC3	ENST00000268184.11	c.1501G>A	p.Gly501Ser	missense_variant	Exon 13 of 15	1	NM_022769.5	ENSP00000268184.6
CRTC3	ENST00000420329.6	c.1501G>A	p.Gly501Ser	missense_variant	Exon 13 of 15	2		ENSP00000416573.2
CRTC3	ENST00000686240.1	n.*914G>A		non_coding_transcript_exon_variant	Exon 12 of 14			ENSP00000508866.1
CRTC3	ENST00000691029.1	n.1501G>A		non_coding_transcript_exon_variant	Exon 13 of 17			ENSP00000510507.1
CRTC3	ENST00000692149.1	n.*828G>A		non_coding_transcript_exon_variant	Exon 11 of 13			ENSP00000510448.1
CRTC3	ENST00000686240.1	n.*914G>A		3_prime_UTR_variant	Exon 12 of 14			ENSP00000508866.1
CRTC3	ENST00000692149.1	n.*828G>A		3_prime_UTR_variant	Exon 11 of 13			ENSP00000510448.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251482 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135922

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	18
DANN	Benign	0.86
DEOGEN2	Benign	0.054	.;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.052	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.32	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.31	N;N
REVEL	Benign	0.10
Sift	Benign	0.42	T;T
Sift4G	Benign	0.42	T;T
Polyphen		0.0	B;B
Vest4		0.095
MutPred		0.18		Gain of phosphorylation at G501 (P = 0.055);Gain of phosphorylation at G501 (P = 0.055);
MVP		0.043
MPC		0.044
ClinPred		0.067	T
GERP RS		0.78
Varity_R		0.043
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs201346508; hg19: chr15-91182000;