rs1554651400

Positions:

• chr9-35658019-A-ACGTCCTCAGCTTC
• chr9-35658019-A-ACGTCCTCAGCTT
• chr9-35658019-A-ACGTCCTCAGCTTCGTCCTCAGCTT

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The variant allele was found at a frequency of 0.00000372 in 537,812 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: intergenic_region
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: -1.84

Genes affected

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-35658019-A-ACGTCCTCAGCTTC is Pathogenic according to our data. Variant chr9-35658019-A-ACGTCCTCAGCTTC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 632968.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.35658019_35658020insCGTCCTCAGCTTC		intergenic_region
RMRP	NR_003051.4	n.-1_1insGAAGCTGAGGACG		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RMRP	ENST00000363046.1	n.-3_-2insGAAGCTGAGGACG		upstream_gene_variant		6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000372 AC: 2 AN: 537812 Hom.: 0 Cov.: 0 AF XY: 0.00000345 AC XY: 1 AN XY: 289610

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000648

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Metaphyseal chondrodysplasia, McKusick type Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Nov 15, 2018

Variant summary: RMRP n.-14_-2dup13 variant involves the duplication of 13 nucleotides in the promoter region of RMRP, which is located between the TATA box (-33 to -25) and the transcription initiation site. Multiple duplication variants in this promoter region have been reported pathogenic (internally and in HGMD). The variant was absent in 119274 control chromosomes (gnomAD). To our knowledge, no occurrence of n.-14_-2dup13 in individuals affected with Cartilage-Hair Hypoplasia and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554651400; hg19: chr9-35658016;