6-41934770-CATT-CATTATT

Variant names:

• chr6-41934770-C-CATT
• rs3218110
• NM_001760.5:c.*1169_*1170insAAT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001760.5(CCND3):​c.*1169_*1170insAAT variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 21)
• Consequence: CCND3 NM_001760.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 6 publications found

Genes affected

CCND3 (HGNC:1585): (cyclin D3) The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activtiy is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. The CDK4 activity associated with this cyclin was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001760.5. 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
	CCND3	NM_001760.5	MANE Select	c.*1169_*1170insAAT		downstream_gene	N/A	NP_001751.1	P30281-1
	CCND3	NM_001424052.1		c.*1169_*1170insAAT		downstream_gene	N/A	NP_001410981.1
	CCND3	NM_001287427.2		c.*1169_*1170insAAT		downstream_gene	N/A	NP_001274356.1	Q5T8J1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCND3	ENST00000372991.9	TSL:1 MANE Select	c.*1169_*1170insAAT		downstream_gene	N/A	ENSP00000362082.5	P30281-1
	CCND3	ENST00000372988.8	TSL:1	c.*1169_*1170insAAT		downstream_gene	N/A	ENSP00000362079.4	P30281-2
	CCND3	ENST00000372987.8	TSL:2	c.*1169_*1170insAAT		downstream_gene	N/A	ENSP00000362078.4	Q5T8J1

Frequencies

GnomAD3 genomes Cov.: 21

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs3218110; hg19: chr6-41902508;