chr19-18744111-A-G

Variant names:

• chr19-18744111-A-G
• ENST00000338797.10:c.247A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000338797.10(CRTC1):​c.247A>G​(p.Ser83Gly) 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CRTC1 ENST00000338797.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.570
• Publications: 0 publications found

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]

ACMG classification

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=0.083260566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC1	NM_015321.3	c.243+1085A>G		intron_variant	Intron 2 of 13	ENST00000321949.13	NP_056136.2
CRTC1	NM_001098482.2	c.247A>G	p.Ser83Gly	missense_variant	Exon 3 of 15		NP_001091952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTC1	ENST00000338797.10	c.247A>G	p.Ser83Gly	missense_variant	Exon 3 of 15	1		ENSP00000345001.5
CRTC1	ENST00000321949.13	c.243+1085A>G		intron_variant	Intron 2 of 13	1	NM_015321.3	ENSP00000323332.7
CRTC1	ENST00000594658.5	c.120+1085A>G		intron_variant	Intron 2 of 13	1		ENSP00000468893.1
CRTC1	ENST00000601916.1	c.18+1085A>G		intron_variant	Intron 1 of 9	5		ENSP00000469285.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.247A>G (p.S83G) alteration is located in exon 3 (coding exon 3) of the CRTC1 gene. This alteration results from a A to G substitution at nucleotide position 247, causing the serine (S) at amino acid position 83 to be replaced by a glycine (G). 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
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.57
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.056
Sift	Benign	0.37	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.25		Loss of glycosylation at S83 (P = 0.0104);
MVP		0.26
MPC		1.6
ClinPred		0.054	T
GERP RS		0.13
gMVP		0.45
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

hg19: chr19-18854921;