2-219539616-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024536.6(CHPF):​c.2095G>A​(p.Glu699Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000855 in 1,613,794 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 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. E699Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000083 ( 1 hom. )

Consequence

CHPF
NM_024536.6 missense

Scores

1
8
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.00
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.121162).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHPFNM_024536.6 linkc.2095G>A p.Glu699Lys missense_variant Exon 4 of 4 ENST00000243776.11 NP_078812.3 Q8IZ52-1
CHPFNM_001195731.2 linkc.1609G>A p.Glu537Lys missense_variant Exon 4 of 4 NP_001182660.2 Q8IZ52-4
CHPFXM_011511838.4 linkc.1222G>A p.Glu408Lys 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.2095G>A p.Glu699Lys missense_variant Exon 4 of 4 1 NM_024536.6 ENSP00000243776.6 Q8IZ52-1

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152248
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00403
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:
0.000144
AC:
36
AN:
249868
Hom.:
1
AF XY:
0.000163
AC XY:
22
AN XY:
135338
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00210
Gnomad EAS exome
AF:
0.0000545
Gnomad SAS exome
AF:
0.000261
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000267
Gnomad OTH exome
AF:
0.000328
GnomAD4 exome
AF:
0.0000828
AC:
121
AN:
1461546
Hom.:
1
Cov.:
30
AF XY:
0.000102
AC XY:
74
AN XY:
727112
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00249
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.000301
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152248
Hom.:
0
Cov.:
34
AF XY:
0.0000807
AC XY:
6
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00403
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:
0.000109
Hom.:
0
Bravo
AF:
0.000125
ExAC
AF:
0.000132
AC:
16
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.30
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.10
T;.
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.6
M;.
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-1.4
N;N
REVEL
Benign
0.19
Sift
Uncertain
0.0050
D;D
Sift4G
Uncertain
0.014
D;D
Polyphen
1.0
D;.
Vest4
0.55
MutPred
0.44
Gain of ubiquitination at E699 (P = 0.0104);.;
MVP
0.65
MPC
0.39
ClinPred
0.16
T
GERP RS
4.6
Varity_R
0.34
gMVP
0.51

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: rs149014949; hg19: chr2-220404338; API