9-35658041-G-C

Position:

• chr9-35658041-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The 9-35658041-G-C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 665,924 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (7 hom., cov: 34)
  • Exomes 𝑓: 0.00083 (5 hom.)
• Consequence: RMRP NR_003051.3 upstream_gene
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.12

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 9-35658041-G-C is Benign according to our data. Variant chr9-35658041-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 379905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RMRP	NR_003051.3			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RMRP	ENST00000363046.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.00457 AC: 696 AN: 152148 Hom.: 7 Cov.: 34

Gnomad AFR AF: 0.0157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00145 AC: 164 AN: 113134 Hom.: 3 AF XY: 0.00110 AC XY: 68 AN XY: 61928

Gnomad AFR exome AF: 0.0171

Gnomad AMR exome AF: 0.00208

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000722

Gnomad FIN exome AF: 0.000426

Gnomad NFE exome AF: 0.000116

Gnomad OTH exome AF: 0.000284

GnomAD4 exome AF: 0.000827 AC: 425 AN: 513658 Hom.: 5 Cov.: 0 AF XY: 0.000750 AC XY: 206 AN XY: 274580

Gnomad4 AFR exome AF: 0.0145

Gnomad4 AMR exome AF: 0.00199

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000318

Gnomad4 SAS exome AF: 0.000755

Gnomad4 FIN exome AF: 0.0000920

Gnomad4 NFE exome AF: 0.000200

Gnomad4 OTH exome AF: 0.00146

GnomAD4 genome AF: 0.00457 AC: 696 AN: 152266 Hom.: 7 Cov.: 34 AF XY: 0.00435 AC XY: 324 AN XY: 74472

Gnomad4 AFR AF: 0.0156

Gnomad4 AMR AF: 0.00176

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.0000859 Hom.: 0

Bravo AF: 0.00542

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 11, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Anauxetic dysplasia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.0010
DANN	Benign	0.24

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs188660894; hg19: chr9-35658038;