chr9-35658075-A-G

Variant names:

• chr9-35658075-A-G
• rs3829077
• NM_174923.3:c.-305A>G

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.-305A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 615,678 control chromosomes in the GnomAD database, including 32,828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6164 hom., cov: 33)
  • Exomes 𝑓: 0.33 (26664 hom.)
• Consequence: CCDC107 NM_174923.3 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.88
• Publications: 8 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: G2P, ClinGen, Myriad Women’s Health, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 9-35658075-A-G is Benign according to our data. Variant chr9-35658075-A-G is described in ClinVar as Benign. ClinVar VariationId is 138920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174923.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC107	NM_174923.3	MANE Select	c.-305A>G		upstream_gene	N/A	NP_777583.2	Q8WV48-1
	RMRP	NR_003051.4	MANE Select	n.-56T>C		upstream_gene	N/A
	CCDC107	NM_001195200.2		c.-305A>G		upstream_gene	N/A	NP_001182129.1	Q8WV48-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC107	ENST00000426546.7	TSL:1 MANE Select	c.-305A>G		upstream_gene	N/A	ENSP00000414964.2	Q8WV48-1
	CCDC107	ENST00000378409.7	TSL:1	c.-305A>G		upstream_gene	N/A	ENSP00000367665.3	Q8WV48-5
	CCDC107	ENST00000327351.6	TSL:1	c.-305A>G		upstream_gene	N/A	ENSP00000330327.2	Q8WV48-2

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40452 AN: 151924 Hom.: 6164 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.331 AC: 153551 AN: 463636 Hom.: 26664 Cov.: 0 AF XY: 0.334 AC XY: 81874 AN XY: 244998

African (AFR) AF: 0.117 AC: 1531 AN: 13076

American (AMR) AF: 0.344 AC: 7843 AN: 22810

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 5123 AN: 15266

East Asian (EAS) AF: 0.529 AC: 16325 AN: 30856

South Asian (SAS) AF: 0.375 AC: 18480 AN: 49312

European-Finnish (FIN) AF: 0.340 AC: 10425 AN: 30632

Middle Eastern (MID) AF: 0.338 AC: 691 AN: 2042

European-Non Finnish (NFE) AF: 0.310 AC: 84539 AN: 273072

Other (OTH) AF: 0.323 AC: 8594 AN: 26570

GnomAD4 genome AF: 0.266 AC: 40445 AN: 152042 Hom.: 6164 Cov.: 33 AF XY: 0.271 AC XY: 20122 AN XY: 74316

African (AFR) AF: 0.109 AC: 4543 AN: 41522

American (AMR) AF: 0.328 AC: 5016 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1170 AN: 3470

East Asian (EAS) AF: 0.484 AC: 2498 AN: 5158

South Asian (SAS) AF: 0.371 AC: 1794 AN: 4830

European-Finnish (FIN) AF: 0.334 AC: 3525 AN: 10550

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21065 AN: 67912

Other (OTH) AF: 0.264 AC: 558 AN: 2112

Alfa AF: 0.144 Hom.: 265

Bravo AF: 0.259

Asia WGS AF: 0.412 AC: 1430 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Anauxetic dysplasia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.0010
DANN	Benign	0.59
PhyloP100		-3.9
PromoterAI		-0.046	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs3829077; hg19: chr9-35658072;