NM_022769.5:c.*622C>T

Variant names:

• chr15-90642762-C-T
• rs3743401
• NM_022769.5:c.*622C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022769.5(CRTC3):​c.*622C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 231,372 control chromosomes in the GnomAD database, including 11,990 homozygotes. 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: 𝑓 0.32 (9009 hom., cov: 32)
  • Exomes 𝑓: 0.26 (2981 hom.)
• Consequence: CRTC3 NM_022769.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.500

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC3	NM_022769.5	c.*622C>T		3_prime_UTR_variant	Exon 15 of 15	ENST00000268184.11	NP_073606.3
CRTC3	NM_001042574.3	c.*622C>T		3_prime_UTR_variant	Exon 15 of 15		NP_001036039.1
CRTC3-AS1	NR_120372.1	n.294-1505G>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTC3	ENST00000268184.11	c.*622C>T		3_prime_UTR_variant	Exon 15 of 15	1	NM_022769.5	ENSP00000268184.6
CRTC3	ENST00000420329.6	c.*622C>T		3_prime_UTR_variant	Exon 15 of 15	2		ENSP00000416573.2
CRTC3	ENST00000686240.1	n.*1895C>T		non_coding_transcript_exon_variant	Exon 14 of 14			ENSP00000508866.1
CRTC3	ENST00000691029.1	n.*622C>T		non_coding_transcript_exon_variant	Exon 15 of 17			ENSP00000510507.1
CRTC3	ENST00000692149.1	n.*1806C>T		non_coding_transcript_exon_variant	Exon 13 of 13			ENSP00000510448.1
CRTC3	ENST00000686240.1	n.*1895C>T		3_prime_UTR_variant	Exon 14 of 14			ENSP00000508866.1
CRTC3	ENST00000691029.1	n.*622C>T		3_prime_UTR_variant	Exon 15 of 17			ENSP00000510507.1
CRTC3	ENST00000692149.1	n.*1806C>T		3_prime_UTR_variant	Exon 13 of 13			ENSP00000510448.1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49291 AN: 152084 Hom.: 8996 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.264 AC: 20933 AN: 79170 Hom.: 2981 Cov.: 0 AF XY: 0.259 AC XY: 9480 AN XY: 36560

Gnomad4 AFR exome AF: 0.490

Gnomad4 AMR exome AF: 0.332

Gnomad4 ASJ exome AF: 0.246

Gnomad4 EAS exome AF: 0.325

Gnomad4 SAS exome AF: 0.206

Gnomad4 FIN exome AF: 0.249

Gnomad4 NFE exome AF: 0.233

Gnomad4 OTH exome AF: 0.269

GnomAD4 genome AF: 0.324 AC: 49346 AN: 152202 Hom.: 9009 Cov.: 32 AF XY: 0.326 AC XY: 24275 AN XY: 74424

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.295

Alfa AF: 0.250 Hom.: 8165

Bravo AF: 0.338

Asia WGS AF: 0.298 AC: 1032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.67

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: rs3743401; hg19: chr15-91185994; COSMIC: COSV51598684; COSMIC: COSV51598684;