Genetic Variant CRTC1:p.Pro393Ser (chr19-18768650-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015321.3(CRTC1):c.1177C>T(p.Pro393Ser) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CRTC1
NM_015321.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40

Publications

0 publications found

Variant links:

Genes affected

CRTC1 (HGNC:16062): (CREB regulated transcription coactivator 1) Enables cAMP response element binding protein binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in cytosol; nuclear body; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CRTC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15111804).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015321.3. 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
	CRTC1	NM_015321.3	MANE Select	c.1177C>T	p.Pro393Ser	missense	Exon 10 of 14	NP_056136.2	Q6UUV9-1
	CRTC1	NM_001098482.2		c.1225C>T	p.Pro409Ser	missense	Exon 11 of 15	NP_001091952.1	Q6UUV9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRTC1	ENST00000321949.13	TSL:1 MANE Select	c.1177C>T	p.Pro393Ser	missense	Exon 10 of 14	ENSP00000323332.7	Q6UUV9-1
CRTC1	ENST00000338797.10	TSL:1	c.1225C>T	p.Pro409Ser	missense	Exon 11 of 15	ENSP00000345001.5	Q6UUV9-2
CRTC1	ENST00000594658.5	TSL:1	c.1054C>T	p.Pro352Ser	missense	Exon 10 of 14	ENSP00000468893.1	M0QX46

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1374514

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

678646

African (AFR)

AF:

0.00

AC:

AN:

30650

American (AMR)

AF:

0.00

AC:

AN:

35442

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24744

East Asian (EAS)

AF:

0.00

AC:

AN:

35388

South Asian (SAS)

AF:

0.00

AC:

AN:

78472

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47646

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4066

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1061192

Other (OTH)

AF:

0.00

AC:

AN:

56914

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.16

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.70

M_CAP

Benign

0.041

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

2.4

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.85

REVEL

Benign

0.072

Sift

Benign

0.31

Sift4G

Benign

0.90

Polyphen

0.0010

Vest4

0.41

MutPred

0.26

Gain of phosphorylation at P393 (P = 0.0031)

MVP

0.20

MPC

0.60

ClinPred

0.15

GERP RS

2.1

Varity_R

0.046

gMVP

0.22

Mutation Taster

=80/20

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over