chr2-219539435-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_024536.6(CHPF):​c.2276G>A​(p.Arg759Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000285 in 1,611,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

CHPF
NM_024536.6 missense

Scores

6
6
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.10
Variant links:
Genes affected
CHPF (HGNC:24291): (chondroitin polymerizing factor) Enables N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase activity and glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase activity. Involved in chondroitin sulfate biosynthetic process. Predicted to be located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.778

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHPFNM_024536.6 linkc.2276G>A p.Arg759Gln missense_variant Exon 4 of 4 ENST00000243776.11 NP_078812.3 Q8IZ52-1
CHPFNM_001195731.2 linkc.1790G>A p.Arg597Gln missense_variant Exon 4 of 4 NP_001182660.2 Q8IZ52-4
CHPFXM_011511838.4 linkc.1403G>A p.Arg468Gln missense_variant Exon 3 of 3 XP_011510140.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHPFENST00000243776.11 linkc.2276G>A p.Arg759Gln missense_variant Exon 4 of 4 1 NM_024536.6 ENSP00000243776.6 Q8IZ52-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152200
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000282
AC:
7
AN:
248376
Hom.:
0
AF XY:
0.0000223
AC XY:
3
AN XY:
134556
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:
0.0000628
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000288
AC:
42
AN:
1459678
Hom.:
0
Cov.:
30
AF XY:
0.0000303
AC XY:
22
AN XY:
725864
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000324
Gnomad4 OTH exome
AF:
0.0000664
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152200
Hom.:
0
Cov.:
34
AF XY:
0.0000269
AC XY:
2
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000476
Hom.:
0
Bravo
AF:
0.0000189
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000247
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 23, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2276G>A (p.R759Q) alteration is located in exon 4 (coding exon 4) of the CHPF gene. This alteration results from a G to A substitution at nucleotide position 2276, causing the arginine (R) at amino acid position 759 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
0.17
BayesDel_addAF
Benign
-0.034
T
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.32
T;.
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Benign
0.048
D
MetaRNN
Pathogenic
0.78
D;D
MetaSVM
Benign
-0.84
T
MutationAssessor
Pathogenic
3.0
M;.
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-3.1
D;D
REVEL
Uncertain
0.43
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.0080
D;D
Polyphen
1.0
D;.
Vest4
0.59
MVP
0.61
MPC
0.88
ClinPred
0.92
D
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.68
gMVP
0.61

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

LitVar

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

Other links and lift over

dbSNP: rs11556310; hg19: chr2-220404157; COSMIC: COSV105033879; COSMIC: COSV105033879; API