rs188660894

Variant names:

• chr9-35658041-G-A
• rs188660894
• ENST00000378409.7:c.-339G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-35658041-G-A
• chr9-35658041-G-C
• chr9-35658041-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000378409.7(CCDC107):​c.-339G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000466 in 665,928 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: 𝑓 0.000085 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: CCDC107 ENST00000378409.7 upstream_gene
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -6.12
• Publications: 0 publications found

Genes affected

CCDC107 (HGNC:28465): (coiled-coil domain containing 107) This gene encodes a membrane protein which contains a coiled-coil domain in the central region. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2013]

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RMRP	NR_003051.4	n.-22C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC107	ENST00000378409.7	c.-339G>A		upstream_gene_variant		1		ENSP00000367665.3
RMRP	ENST00000363046.2	n.-22C>T		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152148 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000530 AC: 6 AN: 113134 AF XY: 0.0000646

Gnomad AFR exome AF: 0.000171

Gnomad AMR exome AF: 0.0000989

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000464

Gnomad OTH exome AF: 0.000284

GnomAD4 exome AF: 0.0000350 AC: 18 AN: 513662 Hom.: 0 Cov.: 0 AF XY: 0.0000510 AC XY: 14 AN XY: 274586

African (AFR) AF: 0.000204 AC: 3 AN: 14716

American (AMR) AF: 0.000163 AC: 5 AN: 30686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18560

East Asian (EAS) AF: 0.0000318 AC: 1 AN: 31398

South Asian (SAS) AF: 0.0000168 AC: 1 AN: 59600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2310

European-Non Finnish (NFE) AF: 0.0000237 AC: 7 AN: 295000

Other (OTH) AF: 0.0000347 AC: 1 AN: 28794

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152266 Hom.: 0 Cov.: 34 AF XY: 0.000107 AC XY: 8 AN XY: 74472

African (AFR) AF: 0.000217 AC: 9 AN: 41552

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000907

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Anauxetic dysplasia Uncertain:1

Sep 26, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant occurs in the RMRP gene, which encodes an RNA molecule that does not result in a protein product. This variant is present in population databases (rs188660894, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RMRP-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.0010
DANN	Benign	0.84
PhyloP100		-6.1
PromoterAI		0.025	Neutral

Splicing

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

Other links and lift over

dbSNP: rs188660894; hg19: chr9-35658038;