Genetic Variant CCHCR1:p.Arg761Ser (chr6-31143300-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001105564.2(CCHCR1):c.2281C>A(p.Arg761Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,416 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R761C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CCHCR1
NM_001105564.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.57

Publications

2 publications found

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]

CCHCR1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCHCR1	NM_001105564.2	MANE Select	c.2281C>A	p.Arg761Ser	missense	Exon 16 of 18	NP_001099034.1	Q8TD31-2
CCHCR1	NM_001394641.1		c.2308C>A	p.Arg770Ser	missense	Exon 16 of 18	NP_001381570.1
CCHCR1	NM_001105563.3		c.2173C>A	p.Arg725Ser	missense	Exon 16 of 18	NP_001099033.1	Q8TD31-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCHCR1	ENST00000396268.8	TSL:1 MANE Select	c.2281C>A	p.Arg761Ser	missense	Exon 16 of 18	ENSP00000379566.3	Q8TD31-2
CCHCR1	ENST00000451521.6	TSL:1	c.2173C>A	p.Arg725Ser	missense	Exon 16 of 18	ENSP00000401039.2	Q8TD31-3
CCHCR1	ENST00000376266.9	TSL:1	c.2014C>A	p.Arg672Ser	missense	Exon 16 of 18	ENSP00000365442.5	Q8TD31-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1460416

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726554

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51990

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1111984

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.060

FATHMM_MKL

Benign

0.22

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

2.6

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-2.3

REVEL

Benign

0.14

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.045

Polyphen

1.0

Vest4

0.63

MutPred

0.46

Gain of phosphorylation at R672 (P = 0.015)

MVP

0.30

MPC

1.4

ClinPred

0.94

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.35

gMVP

0.42

Mutation Taster

=84/16

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over