1-15440369-G-T

Position:

• chr1-15440369-G-T

Variant summary

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

The NM_007272.3(CTRC):​c.110G>T​(p.Arg37Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R37Q) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: CTRC NM_007272.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.893

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=0.12482712).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTRC	NM_007272.3	c.110G>T	p.Arg37Leu	missense_variant	2/8	ENST00000375949.5	NP_009203.2
CTRC	XM_011540550.2	c.110G>T	p.Arg37Leu	missense_variant	2/7		XP_011538852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTRC	ENST00000375949.5	c.110G>T	p.Arg37Leu	missense_variant	2/8	1	NM_007272.3	ENSP00000365116.4
CTRC	ENST00000375943.6	c.40+1865G>T		intron_variant		1		ENSP00000365110.2
CTRC	ENST00000483406.1	n.20G>T		non_coding_transcript_exon_variant	1/6	5
CTRC	ENST00000476813.5	n.52+1865G>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152164 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152164 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74340

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	0.56
DANN	Benign	0.75
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	-0.17	N
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.25
Sift	Benign	0.15	T
Sift4G	Benign	0.25	T
Polyphen		0.0010	B
Vest4		0.27
MutPred		0.48		Loss of disorder (P = 0.0377);
MVP		0.45
MPC		0.25
ClinPred		0.068	T
GERP RS		-4.1
Varity_R		0.30
gMVP		0.55

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: rs145868278; hg19: chr1-15766865;