rs2427556

chr20-63919471-G-Achr20-63919471-G-Cchr20-63919471-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The XM_047440634.1(LOC124904951):c.72G>A(p.Pro24=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 327,970 control chromosomes in the GnomAD database, including 3,790 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 0.23 (2979 hom., cov: 18)
  • Exomes 𝑓: 0.086 (811 hom.)
• Consequence: LOC124904951 XM_047440634.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.818

Genes affected

LOC124904951 (HGNC:):

DNAJC5 (HGNC:16235): (DnaJ heat shock protein family (Hsp40) member C5) This gene is a member of the J protein family. J proteins function in many cellular processes by regulating the ATPase activity of 70 kDa heat shock proteins. The encoded protein plays a role in membrane trafficking and protein folding, and has been shown to have anti-neurodegenerative properties. The encoded protein is known to play a role in cystic fibrosis and Huntington's disease. A pseudogene of this gene is located on the short arm of chromosome 8. [provided by RefSeq, Nov 2010]

MIR941-1 (HGNC:33684): (microRNA 941-1) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR941-2 (HGNC:33685): (microRNA 941-2) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-0.818 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124904951	XM_047440634.1	c.72G>A	p.Pro24=	synonymous_variant	1/1
DNAJC5	NM_025219.3	c.-11-8864G>A		intron_variant		ENST00000360864.9
MIR941-1	NR_030637.3	n.23G>A		non_coding_transcript_exon_variant	1/1
MIR941-2	NR_030638.4			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC5	ENST00000360864.9	c.-11-8864G>A		intron_variant		1	NM_025219.3	P1
MIR941-1	ENST00000636396.1	n.23G>A		non_coding_transcript_exon_variant	1/1
MIR941-2	ENST00000401322.3			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.231 AC: 25107 AN: 108846 Hom.: 2969 Cov.: 18

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.116

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.217

GnomAD3 exomes AF: 0.0289 AC: 3374 AN: 116620 Hom.: 219 AF XY: 0.0226 AC XY: 1507 AN XY: 66712

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.0698

Gnomad ASJ exome AF: 0.0121

Gnomad EAS exome AF: 0.257

Gnomad SAS exome AF: 0.00806

Gnomad FIN exome AF: 0.00166

Gnomad NFE exome AF: 0.0150

Gnomad OTH exome AF: 0.0225

GnomAD4 exome AF: 0.0863 AC: 18896 AN: 219064 Hom.: 811 Cov.: 0 AF XY: 0.0854 AC XY: 11013 AN XY: 128956

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.119

Gnomad4 ASJ exome AF: 0.0394

Gnomad4 EAS exome AF: 0.486

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.0912

Gnomad4 NFE exome AF: 0.0678

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.231 AC: 25136 AN: 108906 Hom.: 2979 Cov.: 18 AF XY: 0.235 AC XY: 12213 AN XY: 51956

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.655

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.219

Alfa AF: 0.256 Hom.: 266

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	6.6
Dann	Benign	0.87

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: rs2427556; hg19: chr20-62550824; COSMIC: COSV62670637; COSMIC: COSV62670637;