6-31143055-T-C

Variant summary

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

The NM_001105564.2(CCHCR1):ā€‹c.2399A>Gā€‹(p.Lys800Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 1,612,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 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: š‘“ 0.00013 ( 0 hom., cov: 32)
Exomes š‘“: 0.00020 ( 0 hom. )

Consequence

CCHCR1
NM_001105564.2 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCHCR1NM_001105564.2 linkuse as main transcriptc.2399A>G p.Lys800Arg missense_variant 17/18 ENST00000396268.8 NP_001099034.1 Q8TD31-2Q769H0Q2TB68

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCHCR1ENST00000396268.8 linkuse as main transcriptc.2399A>G p.Lys800Arg missense_variant 17/181 NM_001105564.2 ENSP00000379566.3 Q8TD31-2

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152142
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000265
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000608
AC:
15
AN:
246592
Hom.:
0
AF XY:
0.0000818
AC XY:
11
AN XY:
134422
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000136
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000201
AC:
294
AN:
1460708
Hom.:
0
Cov.:
36
AF XY:
0.000197
AC XY:
143
AN XY:
726672
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000246
Gnomad4 OTH exome
AF:
0.000331
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152142
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000265
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000262
Hom.:
0
Bravo
AF:
0.0000982
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000185
AC:
1
ExAC
AF:
0.0000424
AC:
5
EpiCase
AF:
0.000273
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 10, 2024The c.2399A>G (p.K800R) alteration is located in exon 17 (coding exon 17) of the CCHCR1 gene. This alteration results from a A to G substitution at nucleotide position 2399, causing the lysine (K) at amino acid position 800 to be replaced by an arginine (R). 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
0.078
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0042
.;T;T;.
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.53
FATHMM_MKL
Benign
0.18
N
LIST_S2
Benign
0.85
.;.;.;D
M_CAP
Benign
0.0065
T
MetaRNN
Benign
0.092
T;T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
2.0
.;M;.;.
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.47
N;N;N;N
REVEL
Benign
0.092
Sift
Uncertain
0.011
D;D;D;D
Sift4G
Benign
0.086
T;D;T;T
Polyphen
0.93
P;P;.;.
Vest4
0.15
MVP
0.27
MPC
0.87
ClinPred
0.17
T
GERP RS
1.9
Varity_R
0.071
gMVP
0.12

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.25
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.25
Position offset: -1

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: rs140279719; hg19: chr6-31110832; API