Variant 7-151235196-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_019015.3(CHPF2):c.412C>T(p.Arg138Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,612,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

CHPF2
NM_019015.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.92

Variant links:

Genes affected

CHPF2 (HGNC:29270): (chondroitin polymerizing factor 2) Predicted to enable glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase activity. Predicted to be involved in chondroitin sulfate biosynthetic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

CHPF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHPF2	NM_019015.3 link	c.412C>T	p.Arg138Trp	missense_variant	2/4	ENST00000035307.7	NP_061888.1	Q9P2E5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHPF2	ENST00000035307.7 link	c.412C>T	p.Arg138Trp	missense_variant	2/4	1	NM_019015.3	ENSP00000035307.2		Q9P2E5-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000799

AC:

AN:

250188

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135276

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1460570

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

726446

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

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 27, 2024

The c.412C>T (p.R138W) alteration is located in exon 2 (coding exon 2) of the CHPF2 gene. This alteration results from a C to T substitution at nucleotide position 412, causing the arginine (R) at amino acid position 138 to be replaced by a tryptophan (W). 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

0.33

BayesDel_addAF

Benign

-0.0046

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.41

.;.;T

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.74

D;D;D

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.5

.;.;M

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-4.4

D;D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.91, 0.90

MutPred

0.65

.;.;Loss of disorder (P = 0.0294);

MVP

0.69

MPC

0.61

ClinPred

1.0

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.52

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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