1-15440524-G-T

Variant names:

• chr1-15440524-G-T
• rs121909294
• NM_007272.3:c.164G>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_007272.3(CTRC):​c.164G>T​(p.Trp55Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CTRC NM_007272.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.88

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.94

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTRC	NM_007272.3	c.164G>T	p.Trp55Leu	missense_variant	Exon 3 of 8	ENST00000375949.5	NP_009203.2
CTRC	XM_011540550.2	c.164G>T	p.Trp55Leu	missense_variant	Exon 3 of 7		XP_011538852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTRC	ENST00000375949.5	c.164G>T	p.Trp55Leu	missense_variant	Exon 3 of 8	1	NM_007272.3	ENSP00000365116.4
CTRC	ENST00000375943.6	c.41-1923G>T		intron_variant	Intron 1 of 4	1		ENSP00000365110.2
CTRC	ENST00000483406.1	n.74G>T		non_coding_transcript_exon_variant	Exon 2 of 6	5
CTRC	ENST00000476813.5	n.53-1923G>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.45	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.087	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Benign	0.090	N
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-8.8	D
REVEL	Uncertain	0.51
Sift	Benign	0.11	T
Sift4G	Benign	0.068	T
Polyphen		1.0	D
Vest4		0.67
MutPred		0.71		Gain of ubiquitination at K51 (P = 0.0685);
MVP		0.89
MPC		0.89
ClinPred		0.80	D
GERP RS		3.1
Varity_R		0.71
gMVP		0.63

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: rs121909294; hg19: chr1-15767020;