6-31144729-C-G

Variant names:

• chr6-31144729-C-G
• rs772907679
• NM_001105564.2:c.2125G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001105564.2(CCHCR1):​c.2125G>C​(p.Glu709Gln) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E709K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CCHCR1 NM_001105564.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.76
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31285757).

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.2125G>C	p.Glu709Gln	missense	Exon 15 of 18	NP_001099034.1	Q8TD31-2
	CCHCR1	NM_001394641.1		c.2152G>C	p.Glu718Gln	missense	Exon 15 of 18	NP_001381570.1
	CCHCR1	NM_001105563.3		c.2017G>C	p.Glu673Gln	missense	Exon 15 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.2125G>C	p.Glu709Gln	missense	Exon 15 of 18	ENSP00000379566.3	Q8TD31-2
	CCHCR1	ENST00000451521.6	TSL:1	c.2017G>C	p.Glu673Gln	missense	Exon 15 of 18	ENSP00000401039.2	Q8TD31-3
	CCHCR1	ENST00000376266.9	TSL:1	c.1858G>C	p.Glu620Gln	missense	Exon 15 of 18	ENSP00000365442.5	Q8TD31-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.085
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.8
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.065
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.075	T
Polyphen		0.97	D
Vest4		0.44
MutPred		0.45		Gain of MoRF binding (P = 0.0599)
MVP		0.29
MPC		1.2
ClinPred		0.78	D
GERP RS		3.1
Varity_R		0.046
gMVP		0.38
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs772907679; hg19: chr6-31112506;