chr1-15438490-C-A

Variant names:

• chr1-15438490-C-A
• rs772818172
• NM_007272.3:c.26C>A

Variant summary

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

The NM_007272.3(CTRC):​c.26C>A​(p.Ala9Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A9V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTRC NM_007272.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.496
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hereditary chronic pancreatitis

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007272.3. 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
	CTRC	NM_007272.3	MANE Select	c.26C>A	p.Ala9Glu	missense	Exon 1 of 8	NP_009203.2	Q99895

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTRC	ENST00000375949.5	TSL:1 MANE Select	c.26C>A	p.Ala9Glu	missense	Exon 1 of 8	ENSP00000365116.4	Q99895
	CTRC	ENST00000375943.6	TSL:1	c.26C>A	p.Ala9Glu	missense	Exon 1 of 5	ENSP00000365110.2	Q68DR9
	CTRC	ENST00000476813.5	TSL:3	n.38C>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Hereditary pancreatitis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.65	T
M_CAP	Uncertain	0.25	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	-0.016	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.50
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.48
Sift	Benign	0.048	D
Sift4G	Uncertain	0.045	D
Polyphen		0.96	D
Vest4		0.37
MutPred		0.59		Loss of helix (P = 0.0167)
MVP		0.96
MPC		0.41
ClinPred		0.69	D
GERP RS		4.4
PromoterAI		-0.0071	Neutral
Varity_R		0.15
gMVP		0.48
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs772818172; hg19: chr1-15764986;