1-15445676-G-C

Position:

• chr1-15445676-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007272.3(CTRC):​c.719G>C​(p.Arg240Pro) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R240Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CTRC NM_007272.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183

Genes affected

CTRC (HGNC:2523): (chymotrypsin C) This gene encodes a member of the peptidase S1 family. The encoded protein is a serum calcium-decreasing factor that has chymotrypsin-like protease activity. Alternatively spliced transcript variants have been observed, but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

CTRC (HGNC:):

ACMG classification

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=0.07957333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTRC	NM_007272.3	c.719G>C	p.Arg240Pro	missense_variant	7/8	ENST00000375949.5	NP_009203.2
CTRC	XM_011540550.2	c.573G>C	p.Pro191Pro	synonymous_variant	6/7		XP_011538852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTRC	ENST00000375949.5	c.719G>C	p.Arg240Pro	missense_variant	7/8	1	NM_007272.3	ENSP00000365116.4
CTRC	ENST00000375943.6	c.*173G>C		3_prime_UTR_variant	4/5	1		ENSP00000365110.2
CTRC	ENST00000483406.1	n.483G>C		non_coding_transcript_exon_variant	5/6	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	2.3
DANN	Benign	0.59
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	-0.015	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.38	N
REVEL	Benign	0.24
Sift	Benign	0.11	T
Sift4G	Benign	0.16	T
Polyphen		0.0	B
Vest4		0.27
MutPred		0.44		Loss of MoRF binding (P = 7e-04);
MVP		0.48
MPC		0.26
ClinPred		0.081	T
GERP RS		1.6
Varity_R		0.27
gMVP		0.78

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: rs760962602; hg19: chr1-15772171;