rs12625454

Positions:

• chr20-63919928-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The XM_047440634.1(LOC124904951):​c.529C>G​(p.His177Asp) 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 0.0017 (0 hom., cov: 3)
  • Exomes 𝑓: 0.0040 (16 hom.)
  • Failed GnomAD Quality Control
• Consequence: LOC124904951 XM_047440634.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.988

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]

MIR941-5 (HGNC:50845): (microRNA 941-5) 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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124904951	XM_047440634.1	c.529C>G	p.His177Asp	missense_variant	1/1
DNAJC5	NM_025219.3	c.-11-8407C>G		intron_variant		ENST00000360864.9
MIR941-5	NR_128719.1	n.61C>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC5	ENST00000360864.9	c.-11-8407C>G		intron_variant		1	NM_025219.3	P1
MIR941-5	ENST00000621667.1	n.61C>G		mature_miRNA_variant	1/1
DNAJC5	ENST00000470551.1	c.-11-8407C>G		intron_variant, NMD_transcript_variant		2
DNAJC5	ENST00000703637.1	c.-418C>G		5_prime_UTR_variant, NMD_transcript_variant	1/6

Frequencies

GnomAD3 genomes AF: 0.00172 AC: 33 AN: 19166 Hom.: 0 Cov.: 3

Gnomad AFR AF: 0.000851

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00112

Gnomad ASJ AF: 0.00110

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0102

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00159

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000290 AC: 47 AN: 161882 Hom.: 0 AF XY: 0.000185 AC XY: 17 AN XY: 92094

Gnomad AFR exome AF: 0.000121

Gnomad AMR exome AF: 0.000431

Gnomad ASJ exome AF: 0.000117

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000119

Gnomad FIN exome AF: 0.000446

Gnomad NFE exome AF: 0.000321

Gnomad OTH exome AF: 0.000903

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00403 AC: 931 AN: 230804 Hom.: 16 Cov.: 0 AF XY: 0.00320 AC XY: 431 AN XY: 134794

Gnomad4 AFR exome AF: 0.000601

Gnomad4 AMR exome AF: 0.00169

Gnomad4 ASJ exome AF: 0.00199

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000968

Gnomad4 FIN exome AF: 0.0155

Gnomad4 NFE exome AF: 0.00515

Gnomad4 OTH exome AF: 0.00376

GnomAD4 genome AF: 0.00172 AC: 33 AN: 19168 Hom.: 0 Cov.: 3 AF XY: 0.00216 AC XY: 20 AN XY: 9238

Gnomad4 AFR AF: 0.000848

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00110

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0102

Gnomad4 NFE AF: 0.00159

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0199 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.9
DANN	Benign	0.53

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: rs12625454; hg19: chr20-62551281; COSMIC: COSV62670891; COSMIC: COSV62670891;