rs12551232

Variant names:

• chr9-35658073-T-A
• rs12551232
• NM_174923.3:c.-307T>A

Your query was ambiguous. Multiple possible variants found:

• chr9-35658073-T-A
• chr9-35658073-T-C
• chr9-35658073-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_174923.3(CCDC107):​c.-307T>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 462,030 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: 0.0000022 (0 hom.)
• Consequence: CCDC107 NM_174923.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.17
• 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 -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
CCDC107	NM_174923.3	c.-307T>A		upstream_gene_variant		ENST00000426546.7	NP_777583.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC107	ENST00000426546.7	c.-307T>A		upstream_gene_variant		1	NM_174923.3	ENSP00000414964.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000216 AC: 1 AN: 462030 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 244354

African (AFR) AF: 0.00 AC: 0 AN: 13080

American (AMR) AF: 0.00 AC: 0 AN: 22372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15176

East Asian (EAS) AF: 0.00 AC: 0 AN: 30802

South Asian (SAS) AF: 0.00 AC: 0 AN: 49142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2050

European-Non Finnish (NFE) AF: 0.00000367 AC: 1 AN: 272362

Other (OTH) AF: 0.00 AC: 0 AN: 26486

GnomAD4 genome Cov.: 34

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
DANN	Benign	0.50
PhyloP100		-6.2
PromoterAI		0.0065	Neutral

Splicing

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

Other links and lift over

dbSNP: rs12551232; hg19: chr9-35658070;