chr15-90619750-C-T

Variant names:

• chr15-90619750-C-T
• rs780188941
• NM_022769.5:c.709C>T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_022769.5(CRTC3):​c.709C>T​(p.Leu237Leu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRTC3 NM_022769.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77

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

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=1.77 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC3	NM_022769.5	c.709C>T	p.Leu237Leu	synonymous_variant	Exon 9 of 15	ENST00000268184.11	NP_073606.3
CRTC3	NM_001042574.3	c.709C>T	p.Leu237Leu	synonymous_variant	Exon 9 of 15		NP_001036039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTC3	ENST00000268184.11	c.709C>T	p.Leu237Leu	synonymous_variant	Exon 9 of 15	1	NM_022769.5	ENSP00000268184.6
CRTC3	ENST00000420329.6	c.709C>T	p.Leu237Leu	synonymous_variant	Exon 9 of 15	2		ENSP00000416573.2
CRTC3	ENST00000558005.1	c.364C>T	p.Leu122Leu	synonymous_variant	Exon 6 of 7	4		ENSP00000452676.1
CRTC3	ENST00000686240.1	n.*122C>T		non_coding_transcript_exon_variant	Exon 8 of 14			ENSP00000508866.1
CRTC3	ENST00000691029.1	n.709C>T		non_coding_transcript_exon_variant	Exon 9 of 17			ENSP00000510507.1
CRTC3	ENST00000692149.1	n.*36C>T		non_coding_transcript_exon_variant	Exon 7 of 13			ENSP00000510448.1
CRTC3	ENST00000686240.1	n.*122C>T		3_prime_UTR_variant	Exon 8 of 14			ENSP00000508866.1
CRTC3	ENST00000692149.1	n.*36C>T		3_prime_UTR_variant	Exon 7 of 13			ENSP00000510448.1
CRTC3	ENST00000687075.1	n.522+1782C>T		intron_variant	Intron 7 of 8			ENSP00000510590.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251456 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135902

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	7.2
DANN	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs780188941; hg19: chr15-91162982; COSMIC: COSV105092088; COSMIC: COSV105092088;