6-31143322-C-G

Variant names:

• chr6-31143322-C-G
• rs1206034207
• NM_001105564.2:c.2259G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001105564.2(CCHCR1):​c.2259G>C​(p.Glu753Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCHCR1 NM_001105564.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00200
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24347478).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105564.2. 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
	CCHCR1	NM_001105564.2	MANE Select	c.2259G>C	p.Glu753Asp	missense	Exon 16 of 18	NP_001099034.1	Q8TD31-2
	CCHCR1	NM_001394641.1		c.2286G>C	p.Glu762Asp	missense	Exon 16 of 18	NP_001381570.1
	CCHCR1	NM_001105563.3		c.2151G>C	p.Glu717Asp	missense	Exon 16 of 18	NP_001099033.1	Q8TD31-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCHCR1	ENST00000396268.8	TSL:1 MANE Select	c.2259G>C	p.Glu753Asp	missense	Exon 16 of 18	ENSP00000379566.3	Q8TD31-2
	CCHCR1	ENST00000451521.6	TSL:1	c.2151G>C	p.Glu717Asp	missense	Exon 16 of 18	ENSP00000401039.2	Q8TD31-3
	CCHCR1	ENST00000376266.9	TSL:1	c.1992G>C	p.Glu664Asp	missense	Exon 16 of 18	ENSP00000365442.5	Q8TD31-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460560 Hom.: 0 Cov.: 37 AF XY: 0.00000138 AC XY: 1 AN XY: 726600

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111944

Other (OTH) AF: 0.0000166 AC: 1 AN: 60382

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T
Eigen	Benign	0.0065
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.58	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.0020
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.12
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.36
MutPred		0.49		Gain of helix (P = 0.0861)
MVP		0.22
MPC		1.2
ClinPred		0.87	D
GERP RS		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.13
gMVP		0.20
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs1206034207; hg19: chr6-31111099;