Genetic Variant RMRP:n.-8T>A (chr9-35658027-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000363046.2(RMRP):n.-8T>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000375 in 533,454 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: 0.0000037 ( 0 hom. )

Consequence

RMRP
ENST00000363046.2 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -9.77

Publications

0 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

RMRP links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RMRP	NR_003051.4 link	n.-8T>A		upstream_gene_variant		ENST00000363046.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RMRP	ENST00000363046.2 link	n.-8T>A		upstream_gene_variant		6	NR_003051.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000375

AC:

AN:

533454

Hom.:

Cov.:

AF XY:

0.00000698

AC XY:

AN XY:

286734

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15382

American (AMR)

AF:

0.00

AC:

AN:

33836

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19578

East Asian (EAS)

AF:

0.00

AC:

AN:

31716

South Asian (SAS)

AF:

0.0000161

AC:

AN:

62044

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33022

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2392

European-Non Finnish (NFE)

AF:

0.00000327

AC:

AN:

305772

Other (OTH)

AF:

0.00

AC:

AN:

29712

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.0010

(source)

DANN

Benign

0.39

PhyloP100

-9.8

PromoterAI

0.021

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over