chr2-219539499-C-A

Variant names:

• chr2-219539499-C-A
• rs148389410
• NM_024536.6:c.2212G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024536.6(CHPF):​c.2212G>T​(p.Ala738Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. A738T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CHPF NM_024536.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.16
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22248614).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024536.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHPF	NM_024536.6	MANE Select	c.2212G>T	p.Ala738Ser	missense	Exon 4 of 4	NP_078812.3
	CHPF	NM_001195731.2		c.1726G>T	p.Ala576Ser	missense	Exon 4 of 4	NP_001182660.2	Q8IZ52-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHPF	ENST00000243776.11	TSL:1 MANE Select	c.2212G>T	p.Ala738Ser	missense	Exon 4 of 4	ENSP00000243776.6	Q8IZ52-1
	CHPF	ENST00000691864.1		c.2188G>T	p.Ala730Ser	missense	Exon 4 of 4	ENSP00000509104.1	A0A8I5QJC8
	CHPF	ENST00000919936.1		c.2134G>T	p.Ala712Ser	missense	Exon 4 of 4	ENSP00000589995.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461342 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727008

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53158

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111850

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.021
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N
PhyloP100		7.2
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.088
Sift	Benign	0.14	T
Sift4G	Benign	0.14	T
Polyphen		0.13	B
Vest4		0.21
MutPred		0.52		Gain of disorder (P = 0.0184)
MVP		0.36
MPC		0.23
ClinPred		0.93	D
GERP RS		4.6
Varity_R		0.083
gMVP		0.34
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs148389410; hg19: chr2-220404221;