rs182194192

Variant names:

• chr21-33488465-C-G
• rs182194192
• NM_001040192.3:c.929G>C

Your query was ambiguous. Multiple possible variants found:

• chr21-33488465-C-G
• chr21-33488465-C-T

Variant summary

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

The NM_001040192.3(DNAJC28):​c.929G>C​(p.Arg310Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. R310Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAJC28 NM_001040192.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.57
• Publications: 6 publications found

Genes affected

DNAJC28 (HGNC:1297): (DnaJ heat shock protein family (Hsp40) member C28) This gene encodes a member of the DnaJ heat shock protein family. The encoded protein, which contains a conserved N-terminal DnaJ domain, is thought to play a role in protein folding or act as a molecular chaperone protein. [provided by RefSeq, Oct 2016]

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, 0.786

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC28	NM_001040192.3	c.929G>C	p.Arg310Pro	missense_variant	Exon 2 of 2	ENST00000381947.4	NP_001035282.1
DNAJC28	NM_001320746.3	c.929G>C	p.Arg310Pro	missense_variant	Exon 2 of 2		NP_001307675.1
DNAJC28	NM_017833.5	c.929G>C	p.Arg310Pro	missense_variant	Exon 2 of 2		NP_060303.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC28	ENST00000381947.4	c.929G>C	p.Arg310Pro	missense_variant	Exon 2 of 2	1	NM_001040192.3	ENSP00000371373.3
DNAJC28	ENST00000314399.3	c.929G>C	p.Arg310Pro	missense_variant	Exon 2 of 2	1		ENSP00000320303.3
DNAJC28	ENST00000402202.1	c.929G>C	p.Arg310Pro	missense_variant	Exon 2 of 2	5		ENSP00000385777.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T;T;T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Benign	0.0091	T
MetaRNN	Pathogenic	0.79	D;D;D;D
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.8	M;M;M;M
PhyloP100		2.6
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.7	.;D;D;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0060	.;D;D;D
Sift4G	Uncertain	0.023	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.65
MutPred		0.51		Gain of sheet (P = 4e-04);Gain of sheet (P = 4e-04);Gain of sheet (P = 4e-04);Gain of sheet (P = 4e-04);
MVP		0.57
MPC		0.28
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.69
gMVP		0.89
Mutation Taster		=52/48	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: rs182194192; hg19: chr21-34860772;