NM_001105564.2:c.2282G>C

Variant names:

• chr6-31143299-C-G
• rs112520959
• NM_001105564.2:c.2282G>C

Variant summary

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

The NM_001105564.2(CCHCR1):​c.2282G>C​(p.Arg761Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCHCR1 NM_001105564.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83

Genes affected

CCHCR1 (HGNC:13930): (coiled-coil alpha-helical rod protein 1) This gene encodes a protein with five coiled-coil alpha-helical rod domains that is thought to act as a regulator of mRNA metabolism through its interaction with mRNA-decapping protein 4. It localizes to P-bodies, the site of mRNA metabolism, with an N-terminus that is required for this subcellular localization, suggesting it is a P-body component. Naturally occurring mutations in this gene are associated with psoriasis. [provided by RefSeq, May 2017]

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
CCHCR1	NM_001105564.2	c.2282G>C	p.Arg761Pro	missense_variant	Exon 16 of 18	ENST00000396268.8	NP_001099034.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCHCR1	ENST00000396268.8	c.2282G>C	p.Arg761Pro	missense_variant	Exon 16 of 18	1	NM_001105564.2	ENSP00000379566.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	.;T;T;.
Eigen	Benign	-0.042
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.25	N
LIST_S2	Uncertain	0.91	.;.;.;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.65	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	.;M;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.2	D;D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.034	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.66
MutPred		0.51		.;Loss of MoRF binding (P = 0.0033);.;.;
MVP		0.27
MPC		1.6
ClinPred		0.98	D
GERP RS		2.2
Varity_R		0.43
gMVP		0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs112520959; hg19: chr6-31111076;