chr15-90625927-A-T

Position:

chr15-90625927-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022769.5(CRTC3):c.901A>T(p.Ser301Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000601 in 1,614,144 control chromosomes in the GnomAD database, including 1 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 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000064 ( 1 hom. )

Consequence

CRTC3
NM_022769.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.22

Variant links:

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 links:

CRTC3 (HGNC:):

CRTC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20075282).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRTC3	NM_022769.5 linkuse as main transcript	c.901A>T	p.Ser301Cys	missense_variant	10/15	ENST00000268184.11	NP_073606.3	Q6UUV7-1Q8TEF4
CRTC3	NM_001042574.3 linkuse as main transcript	c.901A>T	p.Ser301Cys	missense_variant	10/15		NP_001036039.1	Q6UUV7-3Q8TEF4
CRTC3-AS1	NR_120372.1 linkuse as main transcript	n.510-5774T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CRTC3	ENST00000268184.11 linkuse as main transcript	c.901A>T	p.Ser301Cys	missense_variant	10/15	1	NM_022769.5	ENSP00000268184.6	Q6UUV7-1
CRTC3	ENST00000420329.6 linkuse as main transcript	c.901A>T	p.Ser301Cys	missense_variant	10/15	2		ENSP00000416573.2	Q6UUV7-3
CRTC3	ENST00000558005.1 linkuse as main transcript	c.556A>T	p.Ser186Cys	missense_variant	7/7	4		ENSP00000452676.1	H0YK64
CRTC3	ENST00000686240.1 linkuse as main transcript	n.*314A>T		non_coding_transcript_exon_variant	9/14			ENSP00000508866.1	A0A8I5KTH9
CRTC3	ENST00000687075.1 linkuse as main transcript	n.*137A>T		non_coding_transcript_exon_variant	8/9			ENSP00000510590.1	A0A8I5QJV4
CRTC3	ENST00000691029.1 linkuse as main transcript	n.901A>T		non_coding_transcript_exon_variant	10/17			ENSP00000510507.1	Q6UUV7-1
CRTC3	ENST00000692149.1 linkuse as main transcript	n.*228A>T		non_coding_transcript_exon_variant	8/13			ENSP00000510448.1	A0A8I5KTH9
CRTC3	ENST00000686240.1 linkuse as main transcript	n.*314A>T		3_prime_UTR_variant	9/14			ENSP00000508866.1	A0A8I5KTH9
CRTC3	ENST00000687075.1 linkuse as main transcript	n.*137A>T		3_prime_UTR_variant	8/9			ENSP00000510590.1	A0A8I5QJV4
CRTC3	ENST00000692149.1 linkuse as main transcript	n.*228A>T		3_prime_UTR_variant	8/13			ENSP00000510448.1	A0A8I5KTH9

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

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:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000155

AC:

AN:

251478

Hom.:

AF XY:

0.000191

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000643

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000866

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00105

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000189

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 25, 2024

The c.901A>T (p.S301C) alteration is located in exon 10 (coding exon 10) of the CRTC3 gene. This alteration results from a A to T substitution at nucleotide position 901, causing the serine (S) at amino acid position 301 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.54

.;D

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.042

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.47

MutationAssessor

Pathogenic

3.0

M;M

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-4.1

D;D

REVEL

Uncertain

0.37

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;D

Vest4

0.59

MutPred

0.51

Loss of disorder (P = 0.0144);Loss of disorder (P = 0.0144);

MVP

0.21

MPC

0.30

ClinPred

0.38

GERP RS

4.5

Varity_R

0.50

gMVP

0.70

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over