rs130067

Positions:

• chr6-31150734-T-A
• chr6-31150734-T-C
• chr6-31150734-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001105564.2(CCHCR1):​c.1092A>T​(p.Glu364Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCHCR1 NM_001105564.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05204916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCHCR1	NM_001105564.2	c.1092A>T	p.Glu364Asp	missense_variant	6/18	ENST00000396268.8	NP_001099034.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCHCR1	ENST00000396268.8	c.1092A>T	p.Glu364Asp	missense_variant	6/18	1	NM_001105564.2	ENSP00000379566	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.7
DANN	Benign	0.97
DEOGEN2	Benign	0.0032	.;T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.60	.;.;.;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.052	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.34	.;N;.;.
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.49	N;N;N;N
REVEL	Benign	0.019
Sift	Benign	0.63	T;T;T;T
Sift4G	Benign	0.24	T;T;T;T
Polyphen		0.0030	B;B;.;.
Vest4		0.087
MutPred		0.20		.;Loss of ubiquitination at K272 (P = 0.1264);Loss of ubiquitination at K272 (P = 0.1264);.;
MVP		0.20
MPC		0.39
ClinPred		0.046	T
GERP RS		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.025
gMVP		0.058

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: rs130067; hg19: chr6-31118511;