9-111631995-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001015882.3(DNAJC25):c.336+252C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,306 control chromosomes in the GnomAD database, including 2,966 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2966 hom., cov: 33)
• Consequence: DNAJC25 NM_001015882.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC25	NM_001015882.3	c.336+252C>G		intron_variant		ENST00000313525.4
DNAJC25-GNG10	NM_004125.4	c.336+252C>G		intron_variant
DNAJC25	NR_037148.2	n.410+252C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC25	ENST00000313525.4	c.336+252C>G		intron_variant		1	NM_001015882.3	P1
DNAJC25	ENST00000447096.1	c.336+252C>G		intron_variant, NMD_transcript_variant		1
DNAJC25	ENST00000463589.5	c.336+252C>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25356 AN: 152186 Hom.: 2963 Cov.: 33

Gnomad AFR AF: 0.0355

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.176

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.166 AC: 25356 AN: 152306 Hom.: 2966 Cov.: 33 AF XY: 0.176 AC XY: 13126 AN XY: 74470

Gnomad4 AFR AF: 0.0354

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.179

Alfa AF: 0.170 Hom.: 325

Bravo AF: 0.161

Asia WGS AF: 0.321 AC: 1116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.54
Dann	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs10817199; hg19: chr9-114394275;