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):ā€‹c.529C>Gā€‹(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: š‘“ 0.0017 ( 0 hom., cov: 3)
Exomes š‘“: 0.0040 ( 16 hom. )
Failed GnomAD Quality Control

Consequence

LOC124904951
XM_047440634.1 missense

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.988
Variant links:
Genes affected
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]

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ACMG classification

Classification made for transcript

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 Protein UniProt
LOC124904951XM_047440634.1 linkuse as main transcriptc.529C>G p.His177Asp missense_variant 1/1 XP_047296590.1
DNAJC5NM_025219.3 linkuse as main transcriptc.-11-8407C>G intron_variant ENST00000360864.9 NP_079495.1
MIR941-5NR_128719.1 linkuse as main transcriptn.61C>G non_coding_transcript_exon_variant 1/1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAJC5ENST00000360864.9 linkuse as main transcriptc.-11-8407C>G intron_variant 1 NM_025219.3 ENSP00000354111 P1Q9H3Z4-1
MIR941-5ENST00000621667.1 linkuse as main transcriptn.61C>G mature_miRNA_variant 1/1
DNAJC5ENST00000470551.1 linkuse as main transcriptc.-11-8407C>G intron_variant, NMD_transcript_variant 2 ENSP00000434744 Q9H3Z4-2
DNAJC5ENST00000703637.1 linkuse as main transcriptc.-418C>G 5_prime_UTR_variant, NMD_transcript_variant 1/6 ENSP00000515413 Q9H3Z4-2

Frequencies

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

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