Genetic Variant NM_006260.5:c.78C>T (chr13-95677333-C-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_006260.5(DNAJC3):c.78C>T(p.Tyr26Tyr) variant causes a synonymous change. The variant allele was found at a frequency of 0.0034 in 1,598,302 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0035 ( 36 hom. )

Consequence

DNAJC3
NM_006260.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.83

Publications

0 publications found

Variant links:

Genes affected

DNAJC3 (HGNC:9439): (DnaJ heat shock protein family (Hsp40) member C3) This gene encodes a protein with multiple tetratricopeptide repeat (TPR) motifs as well as the highly conserved J domain found in DNAJ chaperone family members. It is a member of the tetratricopeptide repeat family of proteins and acts as an inhibitor of the interferon-induced, dsRNA-activated protein kinase (PKR). [provided by RefSeq, Jul 2010]

DNAJC3 links:

DNAJC3-DT (HGNC:39808): (DNAJC3 divergent transcript)

DNAJC3-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 13-95677333-C-T is Benign according to our data. Variant chr13-95677333-C-T is described in ClinVar as Benign. ClinVar VariationId is 710813.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00241 (367/152298) while in subpopulation SAS AF = 0.0166 (80/4830). AF 95% confidence interval is 0.0136. There are 2 homozygotes in GnomAd4. There are 195 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006260.5. 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
	DNAJC3	NM_006260.5	MANE Select	c.78C>T	p.Tyr26Tyr	synonymous	Exon 1 of 12	NP_006251.1	Q13217

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAJC3	ENST00000602402.6	TSL:1 MANE Select	c.78C>T	p.Tyr26Tyr	synonymous	Exon 1 of 12	ENSP00000473631.1	Q13217
DNAJC3	ENST00000947240.1		c.78C>T	p.Tyr26Tyr	synonymous	Exon 1 of 13	ENSP00000617299.1
DNAJC3	ENST00000880232.1		c.78C>T	p.Tyr26Tyr	synonymous	Exon 1 of 13	ENSP00000550291.1

Frequencies

GnomAD3 genomes

AF:

0.00242

AC:

369

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00608

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0172

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.00241

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00389

AC:

902

AN:

231960

AF XY:

0.00482

show subpopulations

Gnomad AFR exome

AF:

0.000231

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00148

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000279

Gnomad NFE exome

AF:

0.00266

Gnomad OTH exome

AF:

0.00436

GnomAD4 exome

AF:

0.00350

AC:

5063

AN:

1446004

Hom.:

Cov.:

AF XY:

0.00395

AC XY:

2843

AN XY:

719372

show subpopulations

African (AFR)

AF:

0.000194

AC:

AN:

30944

American (AMR)

AF:

0.00180

AC:

AN:

43296

Ashkenazi Jewish (ASJ)

AF:

0.00152

AC:

AN:

25576

East Asian (EAS)

AF:

0.0000267

AC:

AN:

37518

South Asian (SAS)

AF:

0.0182

AC:

1536

AN:

84306

European-Finnish (FIN)

AF:

0.000264

AC:

AN:

53062

Middle Eastern (MID)

AF:

0.0134

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00277

AC:

3065

AN:

1105832

Other (OTH)

AF:

0.00413

AC:

247

AN:

59740

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

257

514

770

1027

1284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

272

408

544

680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00241

AC:

367

AN:

152298

Hom.:

Cov.:

AF XY:

0.00262

AC XY:

195

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.000409

AC:

AN:

41572

American (AMR)

AF:

0.00608

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.0166

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00241

AC:

164

AN:

68010

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00232

Hom.:

Bravo

AF:

0.00195

Asia WGS

AF:

0.00404

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

DNAJC3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

3.8

PromoterAI

-0.050

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over