6-31145061-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001105564.2(CCHCR1):​c.1889G>A​(p.Arg630Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000594 in 1,600,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

CCHCR1
NM_001105564.2 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.055714875).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCHCR1NM_001105564.2 linkc.1889G>A p.Arg630Gln missense_variant Exon 14 of 18 ENST00000396268.8 NP_001099034.1 Q8TD31-2Q769H0Q2TB68

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCHCR1ENST00000396268.8 linkc.1889G>A p.Arg630Gln missense_variant Exon 14 of 18 1 NM_001105564.2 ENSP00000379566.3 Q8TD31-2

Frequencies

GnomAD3 genomes
AF:
0.000355
AC:
54
AN:
152100
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00334
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000798
AC:
19
AN:
238234
Hom.:
0
AF XY:
0.0000770
AC XY:
10
AN XY:
129940
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000496
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000547
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000169
GnomAD4 exome
AF:
0.0000283
AC:
41
AN:
1448290
Hom.:
0
Cov.:
35
AF XY:
0.0000333
AC XY:
24
AN XY:
720236
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000472
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.0000233
Gnomad4 FIN exome
AF:
0.0000675
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.0000333
GnomAD4 genome
AF:
0.000355
AC:
54
AN:
152100
Hom.:
0
Cov.:
31
AF XY:
0.000619
AC XY:
46
AN XY:
74278
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00334
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.000366

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 28, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1889G>A (p.R630Q) alteration is located in exon 14 (coding exon 14) of the CCHCR1 gene. This alteration results from a G to A substitution at nucleotide position 1889, causing the arginine (R) at amino acid position 630 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.53
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.012
.;T;T;.
Eigen
Benign
0.17
Eigen_PC
Benign
0.12
FATHMM_MKL
Benign
0.54
D
LIST_S2
Uncertain
0.95
.;.;.;D
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.056
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.3
.;M;.;.
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-0.97
N;N;N;N
REVEL
Benign
0.074
Sift
Benign
0.16
T;T;T;T
Sift4G
Benign
0.37
T;T;T;T
Polyphen
0.99
D;D;.;.
Vest4
0.39
MutPred
0.52
.;Loss of MoRF binding (P = 0.0303);.;.;
MVP
0.28
MPC
1.3
ClinPred
0.23
T
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.046
gMVP
0.27

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs933918624; hg19: chr6-31112838; API