NM_001105564.2:c.1984C>T

Variant names:

• chr6-31144966-G-A
• rs147152245
• NM_001105564.2:c.1984C>T

Variant summary

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

The NM_001105564.2(CCHCR1):​c.1984C>T​(p.Arg662Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000611 in 1,457,796 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R662H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000061 (0 hom.)
• Consequence: CCHCR1 NM_001105564.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.81
• Publications: 1 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.

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.1984C>T	p.Arg662Cys	missense	Exon 14 of 18	NP_001099034.1	Q8TD31-2
	CCHCR1	NM_001394641.1		c.2011C>T	p.Arg671Cys	missense	Exon 14 of 18	NP_001381570.1
	CCHCR1	NM_001105563.3		c.1876C>T	p.Arg626Cys	missense	Exon 14 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.1984C>T	p.Arg662Cys	missense	Exon 14 of 18	ENSP00000379566.3	Q8TD31-2
	CCHCR1	ENST00000451521.6	TSL:1	c.1876C>T	p.Arg626Cys	missense	Exon 14 of 18	ENSP00000401039.2	Q8TD31-3
	CCHCR1	ENST00000376266.9	TSL:1	c.1717C>T	p.Arg573Cys	missense	Exon 14 of 18	ENSP00000365442.5	Q8TD31-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000161 AC: 4 AN: 248278 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000611 AC: 89 AN: 1457796 Hom.: 0 Cov.: 35 AF XY: 0.0000510 AC XY: 37 AN XY: 725428

African (AFR) AF: 0.000239 AC: 8 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49452

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

European-Non Finnish (NFE) AF: 0.0000719 AC: 80 AN: 1111928

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

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	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.41
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0061	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.8
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.22
Sift	Benign	0.042	D
Sift4G	Uncertain	0.044	D
Polyphen		1.0	D
Vest4		0.66
MVP		0.42
MPC		1.5
ClinPred		0.85	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.074
gMVP		0.25
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs147152245; hg19: chr6-31112743;