chr15-90602327-G-A

Variant names:

• chr15-90602327-G-A
• rs147681624
• NM_022769.5:c.355G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_022769.5(CRTC3):​c.355G>A​(p.Asp119Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00012 in 1,574,878 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: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: CRTC3 NM_022769.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.48
• Publications: 4 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26636335).

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.355G>A	p.Asp119Asn	missense	Exon 4 of 15	NP_073606.3	Q6UUV7-1
	CRTC3	NM_001042574.3		c.355G>A	p.Asp119Asn	missense	Exon 4 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.355G>A	p.Asp119Asn	missense	Exon 4 of 15	ENSP00000268184.6	Q6UUV7-1
	CRTC3	ENST00000420329.6	TSL:2	c.355G>A	p.Asp119Asn	missense	Exon 4 of 15	ENSP00000416573.2	Q6UUV7-3
	CRTC3	ENST00000558005.1	TSL:4	c.46G>A	p.Asp16Asn	missense	Exon 2 of 7	ENSP00000452676.1	H0YK64

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152100 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000140 AC: 35 AN: 249542 AF XY: 0.000185

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: 0.000256

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000127 AC: 180 AN: 1422660 Hom.: 0 Cov.: 25 AF XY: 0.000141 AC XY: 100 AN XY: 710078

African (AFR) AF: 0.00 AC: 0 AN: 32660

American (AMR) AF: 0.00 AC: 0 AN: 44388

Ashkenazi Jewish (ASJ) AF: 0.0000387 AC: 1 AN: 25872

East Asian (EAS) AF: 0.00 AC: 0 AN: 39454

South Asian (SAS) AF: 0.000177 AC: 15 AN: 84534

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.000703 AC: 4 AN: 5686

European-Non Finnish (NFE) AF: 0.000134 AC: 144 AN: 1077610

Other (OTH) AF: 0.000271 AC: 16 AN: 59094

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152218 Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74420

African (AFR) AF: 0.00 AC: 0 AN: 41510

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.000191 Hom.: 1

Bravo AF: 0.000110

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000198 AC: 24

EpiCase AF: 0.000164

EpiControl AF: 0.000474

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	Benign	0.14
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.5
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.14
Sift	Benign	0.041	D
Sift4G	Uncertain	0.011	D
Polyphen		0.065	B
Vest4		0.72
MVP		0.21
MPC		0.053
ClinPred		0.18	T
GERP RS		5.4
Varity_R		0.26
gMVP		0.43
Mutation Taster		=75/25	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: rs147681624; hg19: chr15-91145559;