GeneBe

9-35657948-T-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000363046.2(RMRP):​n.72A>C variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.00000912 in 548,096 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
Exomes 𝑓: 0.0000091 ( 0 hom. )

Consequence

RMRP
ENST00000363046.2 non_coding_transcript_exon

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.16

Publications

12 publications found
Variant links:
Genes affected
RMRP (HGNC:10031): (RNA component of mitochondrial RNA processing endoribonuclease) This gene encodes the RNA component of mitochondrial RNA processing endoribonuclease, which cleaves mitochondrial RNA at a priming site of mitochondrial DNA replication. This RNA also interacts with the telomerase reverse transcriptase catalytic subunit to form a distinct ribonucleoprotein complex that has RNA-dependent RNA polymerase activity and produces double-stranded RNAs that can be processed into small interfering RNA. Mutations in this gene are associated with cartilage-hair hypoplasia.[provided by RefSeq, Mar 2010]
RMRP Gene-Disease associations (from GenCC):
  • cartilage-hair hypoplasia
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Myriad Women’s Health, G2P

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.13).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RMRPNR_003051.4 linkn.72A>C non_coding_transcript_exon_variant Exon 1 of 1 ENST00000363046.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RMRPENST00000363046.2 linkn.72A>C non_coding_transcript_exon_variant Exon 1 of 1 6 NR_003051.4

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.00000912
AC:
5
AN:
548096
Hom.:
0
Cov.:
0
AF XY:
0.0000135
AC XY:
4
AN XY:
296794
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
15734
American (AMR)
AF:
0.00
AC:
0
AN:
34708
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
20026
East Asian (EAS)
AF:
0.00
AC:
0
AN:
32104
South Asian (SAS)
AF:
0.00
AC:
0
AN:
62682
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
33194
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2444
European-Non Finnish (NFE)
AF:
0.0000158
AC:
5
AN:
316790
Other (OTH)
AF:
0.00
AC:
0
AN:
30414
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.535
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
34
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.13
CADD
Benign
19
DANN
Benign
0.94
PhyloP100
7.2
PromoterAI
-0.13
Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs199476103; hg19: chr9-35657945; API