rs6089780

chr20-63919527-G-Achr20-63919527-G-C

Variant summary

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

The XM_047440634.1(LOC124904951):c.128G>A(p.Arg43Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (841 hom., cov: 7)
  • Exomes 𝑓: 0.035 (260 hom.)
• Consequence: LOC124904951 XM_047440634.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

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]

MIR941-2 (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]

MIR941-3 (HGNC:33686): (microRNA 941-3) 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]

MIR941-1 (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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124904951	XM_047440634.1	c.128G>A	p.Arg43Gln	missense_variant	1/1
DNAJC5	NM_025219.3	c.-11-8808G>A		intron_variant		ENST00000360864.9
MIR941-2	NR_030638.4	n.23G>A		non_coding_transcript_exon_variant	1/1
MIR941-3	NR_030639.3			upstream_gene_variant
MIR941-1	NR_030637.3			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC5	ENST00000360864.9	c.-11-8808G>A		intron_variant		1	NM_025219.3	P1
MIR941-2	ENST00000401322.3	n.23G>A		non_coding_transcript_exon_variant	1/1
MIR941-3	ENST00000637366.1			upstream_gene_variant
MIR941-1	ENST00000636396.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.107 AC: 6106 AN: 56912 Hom.: 836 Cov.: 7

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0934

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.0510

Gnomad FIN AF: 0.0620

Gnomad MID AF: 0.0481

Gnomad NFE AF: 0.0666

Gnomad OTH AF: 0.112

GnomAD3 exomes AF: 0.0743 AC: 2394 AN: 32222 Hom.: 111 AF XY: 0.0693 AC XY: 1143 AN XY: 16486

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.127

Gnomad ASJ exome AF: 0.0520

Gnomad EAS exome AF: 0.229

Gnomad SAS exome AF: 0.0291

Gnomad FIN exome AF: 0.0164

Gnomad NFE exome AF: 0.0359

Gnomad OTH exome AF: 0.0541

GnomAD4 exome AF: 0.0350 AC: 4885 AN: 139554 Hom.: 260 Cov.: 0 AF XY: 0.0344 AC XY: 2661 AN XY: 77426

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.0569

Gnomad4 ASJ exome AF: 0.0528

Gnomad4 EAS exome AF: 0.198

Gnomad4 SAS exome AF: 0.0216

Gnomad4 FIN exome AF: 0.0263

Gnomad4 NFE exome AF: 0.0321

Gnomad4 OTH exome AF: 0.0474

GnomAD4 genome AF: 0.107 AC: 6117 AN: 56936 Hom.: 841 Cov.: 7 AF XY: 0.110 AC XY: 2899 AN XY: 26358

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.0934

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.0505

Gnomad4 FIN AF: 0.0620

Gnomad4 NFE AF: 0.0666

Gnomad4 OTH AF: 0.112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	7.6
Dann	Benign	0.89

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: rs6089780; hg19: chr20-62550880; COSMIC: COSV62671019; COSMIC: COSV62671019;