rs3130453

Positions:

• chr6-31157072-C-A
• chr6-31157072-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001105564.2(CCHCR1):​c.234G>T​(p.Trp78Cys) 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. 11/18 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: 0.265

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2576583).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCHCR1	NM_001105564.2	c.234G>T	p.Trp78Cys	missense_variant	2/18	ENST00000396268.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCHCR1	ENST00000396268.8	c.234G>T	p.Trp78Cys	missense_variant	2/18	1	NM_001105564.2	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	.;.;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.64	.;T;.
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.00044	P;P;P;P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.4	N;N;D
REVEL	Benign	0.038
Sift	Benign	0.18	T;T;T
Sift4G	Pathogenic	0.0	D;T;.
Polyphen		0.011	B;.;.
Vest4		0.27
MutPred		0.26		Loss of MoRF binding (P = 0.0317);Loss of MoRF binding (P = 0.0317);.;
MVP		0.26
MPC		0.69
ClinPred		0.83	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.072

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3130453; hg19: chr6-31124849;