dbSNP rs1203274006: DNAJC22:p.Met102Ile (chr12-49349178-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001304944.2(DNAJC22):c.306G>A(p.Met102Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DNAJC22
NM_001304944.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.23

Publications

0 publications found

Variant links:

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]

DNAJC22 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.13214114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC22	NM_001304944.2 link	c.306G>A	p.Met102Ile	missense_variant	Exon 3 of 4	ENST00000549441.7	NP_001291873.1	Q8N4W6A0A024R0Z2
DNAJC22	NM_024902.4 link	c.306G>A	p.Met102Ile	missense_variant	Exon 2 of 3		NP_079178.2	Q8N4W6A0A024R0Z2
DNAJC22	XM_047429555.1 link	c.306G>A	p.Met102Ile	missense_variant	Exon 3 of 6		XP_047285511.1
DNAJC22	XM_047429556.1 link	c.306G>A	p.Met102Ile	missense_variant	Exon 3 of 5		XP_047285512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAJC22	ENST00000549441.7 link	c.306G>A	p.Met102Ile	missense_variant	Exon 3 of 4	2	NM_001304944.2	ENSP00000446830.1	Q8N4W6
DNAJC22	ENST00000395069.3 link	c.306G>A	p.Met102Ile	missense_variant	Exon 2 of 3	1		ENSP00000378508.2	Q8N4W6
DNAJC22	ENST00000647553.1 link	n.306G>A		non_coding_transcript_exon_variant	Exon 2 of 4			ENSP00000498036.1	Q8N4W6

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.024

T;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.031

FATHMM_MKL

Uncertain

0.83

M_CAP

Benign

0.0094

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M

PhyloP100

1.2

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.40

N;N

REVEL

Benign

0.033

Sift

Benign

0.45

T;T

Sift4G

Uncertain

0.045

D;D

Polyphen

0.085

B;B

Vest4

0.32

MutPred

0.35

Gain of catalytic residue at S98 (P = 3e-04);Gain of catalytic residue at S98 (P = 3e-04);

MVP

0.32

MPC

0.031

ClinPred

0.28

GERP RS

4.1

Varity_R

0.15

gMVP

0.50

Mutation Taster

=90/10

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over