chr2-219539580-A-T

Position:

• chr2-219539580-A-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_024536.6(CHPF):​c.2131T>A​(p.Phe711Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: CHPF NM_024536.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.42

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 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.952

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHPF	NM_024536.6	c.2131T>A	p.Phe711Ile	missense_variant	4/4	ENST00000243776.11	NP_078812.3
CHPF	NM_001195731.2	c.1645T>A	p.Phe549Ile	missense_variant	4/4		NP_001182660.2
CHPF	XM_011511838.4	c.1258T>A	p.Phe420Ile	missense_variant	3/3		XP_011510140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHPF	ENST00000243776.11	c.2131T>A	p.Phe711Ile	missense_variant	4/4	1	NM_024536.6	ENSP00000243776.6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2023

The c.2131T>A (p.F711I) alteration is located in exon 4 (coding exon 4) of the CHPF gene. This alteration results from a T to A substitution at nucleotide position 2131, causing the phenylalanine (F) at amino acid position 711 to be replaced by an isoleucine (I). 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	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T;.
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.95	D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Pathogenic	3.0	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.011	D;D
Polyphen		1.0	D;.
Vest4		0.85
MutPred		0.88		Gain of phosphorylation at Y708 (P = 0.1041);.;
MVP		0.57
MPC		0.98
ClinPred		1.0	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.72
gMVP		0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-220404302;