9-111649894-C-T

Variant names:

• chr9-111649894-C-T
• rs749436855
• NM_001015882.3:c.931C>T

Variant summary

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

The NM_001015882.3(DNAJC25):​c.931C>T​(p.Arg311*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000625 in 1,441,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: DNAJC25 NM_001015882.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 0 publications found

Genes affected

DNAJC25 (HGNC:34187): (DnaJ heat shock protein family (Hsp40) member C25) Predicted to be involved in protein folding. Predicted to be located in membrane. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC25-GNG10 (HGNC:37501): (DNAJC25-GNG10 readthrough) This gene represents naturally-occurring mRNAs that are co-transcribed products of the neighboring DNAJC25 and GNG10 genes. These transcripts include the first exon of DNAJC25 and the last two exons of GNG10, resulting in a protein that combines the N-terminus of DNAJC25 and the C-terminus of GNG10. [provided by RefSeq, Dec 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001015882.3. 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
	DNAJC25	NM_001015882.3	MANE Select	c.931C>T	p.Arg311*	stop_gained	Exon 3 of 4	NP_001015882.2	Q9H1X3-1
	DNAJC25-GNG10	NM_004125.4		c.337-16921C>T		intron	N/A	NP_004116.2
	DNAJC25	NR_037148.2		n.1243C>T		non_coding_transcript_exon	Exon 4 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC25	ENST00000313525.4	TSL:1 MANE Select	c.931C>T	p.Arg311*	stop_gained	Exon 3 of 4	ENSP00000320650.3	Q9H1X3-1
	DNAJC25-GNG10	ENST00000374294.3	TSL:2	c.337-16921C>T		intron	N/A	ENSP00000363412.3
	DNAJC25	ENST00000447096.1	TSL:1	n.*761C>T		non_coding_transcript_exon	Exon 4 of 5	ENSP00000399325.1	F2Z3D1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000436 AC: 1 AN: 229516 AF XY: 0.00000802

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000625 AC: 9 AN: 1441020 Hom.: 0 Cov.: 32 AF XY: 0.00000838 AC XY: 6 AN XY: 716142

African (AFR) AF: 0.00 AC: 0 AN: 32244

American (AMR) AF: 0.00 AC: 0 AN: 40840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24850

East Asian (EAS) AF: 0.00 AC: 0 AN: 39584

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 82096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4322

European-Non Finnish (NFE) AF: 0.00000724 AC: 8 AN: 1105210

Other (OTH) AF: 0.00 AC: 0 AN: 59322

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.52	D
BayesDel_noAF	Pathogenic	0.62
CADD	Pathogenic	39
DANN	Uncertain	1.0
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.91	D
PhyloP100		1.4
Vest4		0.33
GERP RS		3.9
Mutation Taster		=18/182	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs749436855; hg19: chr9-114412174; COSMIC: COSV57957784;