9-111631995-C-G

Variant names:

• chr9-111631995-C-G
• rs10817199
• NM_001015882.3:c.336+252C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000313525.4(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 ENST00000313525.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 3 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000313525.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC25	NM_001015882.3	MANE Select	c.336+252C>G		intron	N/A	NP_001015882.2
	DNAJC25-GNG10	NM_004125.4		c.336+252C>G		intron	N/A	NP_004116.2
	DNAJC25	NR_037148.2		n.410+252C>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC25	ENST00000313525.4	TSL:1 MANE Select	c.336+252C>G		intron	N/A	ENSP00000320650.3
	DNAJC25-GNG10	ENST00000374294.3	TSL:2	c.336+252C>G		intron	N/A	ENSP00000363412.3
	DNAJC25	ENST00000447096.1	TSL:1	n.336+252C>G		intron	N/A	ENSP00000399325.1

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

African (AFR) AF: 0.0354 AC: 1472 AN: 41584

American (AMR) AF: 0.243 AC: 3722 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3472

East Asian (EAS) AF: 0.491 AC: 2539 AN: 5176

South Asian (SAS) AF: 0.195 AC: 942 AN: 4832

European-Finnish (FIN) AF: 0.292 AC: 3097 AN: 10594

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12113 AN: 68022

Other (OTH) AF: 0.179 AC: 379 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.54
DANN	Benign	0.60
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs10817199; hg19: chr9-114394275;