12-49349374-C-T

Variant names:

• chr12-49349374-C-T
• rs371277828
• NM_001304944.2:c.502C>T

Variant summary

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

The NM_001304944.2(DNAJC22):​c.502C>T​(p.Arg168Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000442 in 1,604,852 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R168H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: DNAJC22 NM_001304944.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.102
• Publications: 0 publications found

Genes affected

DNAJC22 (HGNC:25802): (DnaJ heat shock protein family (Hsp40) member C22) Predicted to be integral component of 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=0.083821386).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304944.2. 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
	DNAJC22	NM_001304944.2	MANE Select	c.502C>T	p.Arg168Cys	missense	Exon 3 of 4	NP_001291873.1	Q8N4W6
	DNAJC22	NM_024902.4		c.502C>T	p.Arg168Cys	missense	Exon 2 of 3	NP_079178.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC22	ENST00000549441.7	TSL:2 MANE Select	c.502C>T	p.Arg168Cys	missense	Exon 3 of 4	ENSP00000446830.1	Q8N4W6
	DNAJC22	ENST00000395069.3	TSL:1	c.502C>T	p.Arg168Cys	missense	Exon 2 of 3	ENSP00000378508.2	Q8N4W6
	DNAJC22	ENST00000851339.1		c.502C>T	p.Arg168Cys	missense	Exon 4 of 5	ENSP00000521398.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000947 AC: 23 AN: 242916 AF XY: 0.000107

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.0000302

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000220

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000136

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000441 AC: 64 AN: 1452520 Hom.: 0 Cov.: 31 AF XY: 0.0000512 AC XY: 37 AN XY: 722094

African (AFR) AF: 0.00 AC: 0 AN: 32990

American (AMR) AF: 0.0000231 AC: 1 AN: 43348

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25444

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39622

South Asian (SAS) AF: 0.000129 AC: 11 AN: 85156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52852

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5720

European-Non Finnish (NFE) AF: 0.0000379 AC: 42 AN: 1107518

Other (OTH) AF: 0.0000835 AC: 5 AN: 59870

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152332 Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2 AN XY: 74492

African (AFR) AF: 0.0000241 AC: 1 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000103 Hom.: 0

Bravo AF: 0.0000416

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000115 AC: 14

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.18	N
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.10
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.057
Sift	Benign	0.060	T
Sift4G	Benign	0.080	T
Polyphen		0.050	B
Vest4		0.21
MVP		0.49
MPC		0.031
ClinPred		0.044	T
GERP RS		1.8
Varity_R		0.17
gMVP		0.71
Mutation Taster		=78/22	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: rs371277828; hg19: chr12-49743157;