rs782665641

Variant names:

• chr17-41977285-C-G
• rs782665641
• NM_003315.4:c.1423G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-41977285-C-G
• chr17-41977285-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003315.4(DNAJC7):​c.1423G>C​(p.Gly475Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. G475S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAJC7 NM_003315.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.70
• Publications: 1 publications found

Genes affected

DNAJC7 (HGNC:12392): (DnaJ heat shock protein family (Hsp40) member C7) This gene encodes a member of the DNAJ heat shock protein 40 family of proteins that is characterized by two N-terminal tetratricopeptide repeat domains and a C-terminal DNAJ domain. This protein binds the chaperone proteins heat shock proteins 70 and 90 in an ATP-dependent manner and may function as a co-chaperone. Pseudogenes of this gene are found on chromosomes 1 and 6. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

CNP (HGNC:2158): (2',3'-cyclic nucleotide 3' phosphodiesterase) Predicted to enable 2',3'-cyclic-nucleotide 3'-phosphodiesterase activity. Involved in substantia nigra development. Located in several cellular components, including extracellular space; microtubule; and plasma membrane. Implicated in hypomyelinating leukodystrophy 20; multiple sclerosis; and schizophrenia. Biomarker of alcoholic liver cirrhosis; multiple sclerosis; and restless legs syndrome. [provided by Alliance of Genome Resources, Apr 2022]

CNP Gene-Disease associations (from GenCC):

• leukodystrophy, hypomyelinating, 20

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.774

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003315.4. 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
	DNAJC7	NM_003315.4	MANE Select	c.1423G>C	p.Gly475Arg	missense	Exon 13 of 14	NP_003306.3	Q99615-1
	CNP	NM_033133.5	MANE Select	c.*3361C>G		3_prime_UTR	Exon 4 of 4	NP_149124.3
	DNAJC7	NM_001144766.3		c.1255G>C	p.Gly419Arg	missense	Exon 13 of 14	NP_001138238.1	Q99615-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC7	ENST00000457167.9	TSL:1 MANE Select	c.1423G>C	p.Gly475Arg	missense	Exon 13 of 14	ENSP00000406463.2	Q99615-1
	DNAJC7	ENST00000316603.12	TSL:1	c.1255G>C	p.Gly419Arg	missense	Exon 12 of 13	ENSP00000313311.7	Q99615-2
	CNP	ENST00000393892.8	TSL:1 MANE Select	c.*3361C>G		3_prime_UTR	Exon 4 of 4	ENSP00000377470.2	P09543-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.7
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.46
Sift	Benign	0.20	T
Sift4G	Benign	0.063	T
Polyphen		0.93	P
Vest4		0.90
MutPred		0.53		Gain of methylation at G475 (P = 0.0076)
MVP		0.84
MPC		0.77
ClinPred		0.93	D
GERP RS		5.7
Varity_R		0.15
gMVP		0.81

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: rs782665641; hg19: chr17-40129303;