NM_004067.4:c.611A>C

Variant names:

• chr7-29480313-A-C
• rs3750103
• NM_004067.4:c.611A>C

Variant summary

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

The NM_004067.4(CHN2):​c.611A>C​(p.His204Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHN2 NM_004067.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.98
• Publications: 0 publications found

Genes affected

CHN2 (HGNC:1944): (chimerin 2) This gene encodes a guanosine triphosphate (GTP)-metabolizing protein that contains a phorbol-ester/diacylglycerol (DAG)-type zinc finger, a Rho-GAP domain, and an SH2 domain. The encoded protein translocates from the cytosol to the Golgi apparatus membrane upon binding by diacylglycerol (DAG). Activity of this protein is important in cell proliferation and migration, and expression changes in this gene have been detected in cancers. A mutation in this gene has also been associated with schizophrenia in men. Alternative transcript splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, May 2014]

PRR15-DT (HGNC:55866): (PRR15 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004067.4. 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
	CHN2	NM_004067.4	MANE Select	c.611A>C	p.His204Pro	missense	Exon 7 of 13	NP_004058.1	P52757-1
	CHN2	NM_001293070.2		c.650A>C	p.His217Pro	missense	Exon 8 of 14	NP_001279999.1	B7Z1V0
	CHN2	NM_001293072.2		c.566A>C	p.His189Pro	missense	Exon 7 of 13	NP_001280001.1	B7Z1W9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHN2	ENST00000222792.11	TSL:1 MANE Select	c.611A>C	p.His204Pro	missense	Exon 7 of 13	ENSP00000222792.7	P52757-1
	CHN2	ENST00000421775.6	TSL:1	c.203A>C	p.His68Pro	missense	Exon 1 of 6	ENSP00000394284.2	P52757-5
	CHN2	ENST00000409041.8	TSL:1	c.203A>C	p.His68Pro	missense	Exon 1 of 5	ENSP00000386849.5	B3VCF5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.076
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	0.69	N
PhyloP100		7.0
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.22
Sift	Benign	0.20	T
Sift4G	Benign	0.067	T
Polyphen		0.013	B
Vest4		0.22
MutPred		0.46		Loss of catalytic residue at N280 (P = 0.0582)
MVP		0.85
MPC		0.50
ClinPred		0.79	D
GERP RS		4.4
PromoterAI		-0.012	Neutral
Varity_R		0.16
gMVP		0.59
Mutation Taster		=79/21	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: rs3750103; hg19: chr7-29519929;