Variant 2-219539577-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024536.6(CHPF):c.2134C>T(p.Leu712Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000178 in 1,613,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

CHPF
NM_024536.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71

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]

CHPF links:

CHPF (HGNC:):

CHPF links:

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=0.16910681).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHPF	NM_024536.6 linkuse as main transcript	c.2134C>T	p.Leu712Phe	missense_variant	4/4	ENST00000243776.11	NP_078812.3	Q8IZ52-1
CHPF	NM_001195731.2 linkuse as main transcript	c.1648C>T	p.Leu550Phe	missense_variant	4/4		NP_001182660.2	Q8IZ52-4
CHPF	XM_011511838.4 linkuse as main transcript	c.1261C>T	p.Leu421Phe	missense_variant	3/3		XP_011510140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHPF	ENST00000243776.11 linkuse as main transcript	c.2134C>T	p.Leu712Phe	missense_variant	4/4	1	NM_024536.6	ENSP00000243776.6		Q8IZ52-1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000323

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000227

AC:

AN:

250586

Hom.:

AF XY:

0.000243

AC XY:

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000371

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000180

AC:

263

AN:

1461548

Hom.:

Cov.:

AF XY:

0.000195

AC XY:

142

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.0000752

Gnomad4 NFE exome

AF:

0.000213

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000158

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.000216

Hom.:

Bravo

AF:

0.000219

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000189

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000474

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 submitter

clinical testing

Ambry Genetics

Sep 22, 2023

The c.2134C>T (p.L712F) alteration is located in exon 4 (coding exon 4) of the CHPF gene. This alteration results from a C to T substitution at nucleotide position 2134, causing the leucine (L) at amino acid position 712 to be replaced by a phenylalanine (F). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;.

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.19

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.017

D;D

Polyphen

1.0

D;.

Vest4

0.24

MVP

0.40

MPC

0.89

ClinPred

0.15

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.084

gMVP

0.63

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over