chr8-103378240-T-C

Variant names:

• chr8-103378240-T-C
• NM_138455.4:c.586T>C

Variant summary

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

The NM_138455.4(CTHRC1):​c.586T>C​(p.Ser196Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTHRC1 NM_138455.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.81

Genes affected

CTHRC1 (HGNC:18831): (collagen triple helix repeat containing 1) This locus encodes a protein that may play a role in the cellular response to arterial injury through involvement in vascular remodeling. Mutations at this locus have been associated with Barrett esophagus and esophageal adenocarcinoma. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTHRC1	NM_138455.4	c.586T>C	p.Ser196Pro	missense_variant	Exon 3 of 4	ENST00000330295.10	NP_612464.1
CTHRC1	NM_001256099.2	c.544T>C	p.Ser182Pro	missense_variant	Exon 3 of 4		NP_001243028.1
CTHRC1	XM_011516824.3	c.372+2281T>C		intron_variant	Intron 2 of 2		XP_011515126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTHRC1	ENST00000330295.10	c.586T>C	p.Ser196Pro	missense_variant	Exon 3 of 4	1	NM_138455.4	ENSP00000330523.5
CTHRC1	ENST00000520337.1	c.544T>C	p.Ser182Pro	missense_variant	Exon 3 of 4	1		ENSP00000430550.1
CTHRC1	ENST00000520880.1	c.196T>C	p.Ser66Pro	missense_variant	Exon 2 of 3	4		ENSP00000430399.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.586T>C (p.S196P) alteration is located in exon 3 (coding exon 3) of the CTHRC1 gene. This alteration results from a T to C substitution at nucleotide position 586, causing the serine (S) at amino acid position 196 to be replaced by a proline (P). 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
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;.;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	2.0	M;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.21
Sift	Uncertain	0.026	D;D;D
Sift4G	Uncertain	0.034	D;T;T
Polyphen		0.97	D;.;.
Vest4		0.85
MutPred		0.21		Loss of disorder (P = 0.1132);.;.;
MVP		0.87
MPC		0.63
ClinPred		0.93	D
GERP RS		5.4
Varity_R		0.31
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-104390468;