9-35658073-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_174923.3(CCDC107):​c.-307T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 613,924 control chromosomes in the GnomAD database, including 6,974 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2806 hom., cov: 34)
  • Exomes 𝑓: 0.12 (4168 hom.)
• Consequence: CCDC107 NM_174923.3 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -6.17
• Publications: 2 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 9-35658073-T-C is Benign according to our data. Variant chr9-35658073-T-C is described in ClinVar as Benign. ClinVar VariationId is 138921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC107	NM_174923.3	c.-307T>C		upstream_gene_variant		ENST00000426546.7	NP_777583.2
RMRP	NR_003051.4	n.-54A>G		upstream_gene_variant		ENST00000363046.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC107	ENST00000426546.7	c.-307T>C		upstream_gene_variant		1	NM_174923.3	ENSP00000414964.2
RMRP	ENST00000363046.2	n.-54A>G		upstream_gene_variant		6	NR_003051.4

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26035 AN: 152034 Hom.: 2789 Cov.: 34

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.0350

Gnomad SAS AF: 0.0892

Gnomad FIN AF: 0.0859

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.123 AC: 57008 AN: 461772 Hom.: 4168 Cov.: 0 AF XY: 0.121 AC XY: 29672 AN XY: 244216

African (AFR) AF: 0.307 AC: 4019 AN: 13070

American (AMR) AF: 0.109 AC: 2430 AN: 22350

Ashkenazi Jewish (ASJ) AF: 0.0742 AC: 1126 AN: 15170

East Asian (EAS) AF: 0.0255 AC: 784 AN: 30796

South Asian (SAS) AF: 0.0941 AC: 4621 AN: 49092

European-Finnish (FIN) AF: 0.0892 AC: 2725 AN: 30558

Middle Eastern (MID) AF: 0.101 AC: 208 AN: 2050

European-Non Finnish (NFE) AF: 0.138 AC: 37663 AN: 272218

Other (OTH) AF: 0.130 AC: 3432 AN: 26468

GnomAD4 genome AF: 0.172 AC: 26099 AN: 152152 Hom.: 2806 Cov.: 34 AF XY: 0.165 AC XY: 12288 AN XY: 74398

African (AFR) AF: 0.308 AC: 12761 AN: 41482

American (AMR) AF: 0.123 AC: 1884 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0700 AC: 243 AN: 3470

East Asian (EAS) AF: 0.0351 AC: 182 AN: 5188

South Asian (SAS) AF: 0.0893 AC: 431 AN: 4826

European-Finnish (FIN) AF: 0.0859 AC: 911 AN: 10610

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.135 AC: 9174 AN: 67956

Other (OTH) AF: 0.165 AC: 349 AN: 2114

Alfa AF: 0.0677 Hom.: 76

Bravo AF: 0.182

Asia WGS AF: 0.0930 AC: 324 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Sep 20, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Metaphyseal chondrodysplasia, McKusick type Benign:1

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Anauxetic dysplasia Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.0010
DANN	Benign	0.38
PhyloP100		-6.2
PromoterAI		0.018	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;