Genetic Variant NM_019015.3:c.295C>T (chr7-151235079-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_019015.3(CHPF2):c.295C>T(p.Arg99Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000571 in 1,575,586 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

CHPF2
NM_019015.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.14

Publications

2 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019015.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHPF2	NM_019015.3	MANE Select	c.295C>T	p.Arg99Cys	missense	Exon 2 of 4	NP_061888.1	Q9P2E5-1
CHPF2	NM_001284295.2		c.271C>T	p.Arg91Cys	missense	Exon 3 of 5	NP_001271224.1	G5E9W2
CHPF2	NM_001389651.1		c.295C>T	p.Arg99Cys	missense	Exon 2 of 3	NP_001376580.1	A0A8I5KRN5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHPF2	ENST00000035307.7	TSL:1 MANE Select	c.295C>T	p.Arg99Cys	missense	Exon 2 of 4	ENSP00000035307.2	Q9P2E5-1
CHPF2	ENST00000495645.5	TSL:2	c.271C>T	p.Arg91Cys	missense	Exon 3 of 5	ENSP00000418914.1	G5E9W2
CHPF2	ENST00000692651.1		c.295C>T	p.Arg99Cys	missense	Exon 2 of 3	ENSP00000509142.1	A0A8I5KRN5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000441

AC:

AN:

226886

AF XY:

0.00000825

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000307

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000562

AC:

AN:

1423284

Hom.:

Cov.:

AF XY:

0.00000285

AC XY:

AN XY:

702102

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32864

American (AMR)

AF:

0.00

AC:

AN:

42350

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23762

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39204

South Asian (SAS)

AF:

0.00

AC:

AN:

80948

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51942

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5608

European-Non Finnish (NFE)

AF:

0.00000551

AC:

AN:

1088002

Other (OTH)

AF:

0.0000171

AC:

AN:

58604

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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

AF:

0.00000657

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41570

American (AMR)

AF:

0.0000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.57

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.064

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.58

MutationAssessor

Uncertain

2.9

PhyloP100

3.1

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-7.6

REVEL

Benign

0.28

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.66

MutPred

0.61

Loss of MoRF binding (P = 0.0271)

MVP

0.66

MPC

0.75

ClinPred

1.0

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.79

gMVP

0.80

Mutation Taster

=38/62

disease causing

(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