6-41935269-T-C

Variant names:

• chr6-41935269-T-C
• rs9529
• NM_001760.5:c.*671A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001760.5(CCND3):​c.*671A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 233,632 control chromosomes in the GnomAD database, including 69,710 homozygotes. 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 0.78 (47424 hom., cov: 34)
  • Exomes 𝑓: 0.74 (22286 hom.)
• Consequence: CCND3 NM_001760.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220
• Publications: 19 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

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.*671A>G		3_prime_UTR	Exon 5 of 5	NP_001751.1	P30281-1
	CCND3	NM_001424052.1		c.*671A>G		3_prime_UTR	Exon 6 of 6	NP_001410981.1
	CCND3	NM_001287427.2		c.*671A>G		3_prime_UTR	Exon 5 of 5	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.*671A>G		3_prime_UTR	Exon 5 of 5	ENSP00000362082.5	P30281-1
	CCND3	ENST00000372988.8	TSL:1	c.*671A>G		3_prime_UTR	Exon 5 of 5	ENSP00000362079.4	P30281-2
	CCND3	ENST00000372987.8	TSL:2	c.*671A>G		3_prime_UTR	Exon 5 of 5	ENSP00000362078.4	Q5T8J1

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119077 AN: 152144 Hom.: 47370 Cov.: 34

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.758

GnomAD4 exome AF: 0.738 AC: 60051 AN: 81370 Hom.: 22286 Cov.: 0 AF XY: 0.738 AC XY: 27643 AN XY: 37440

African (AFR) AF: 0.948 AC: 3693 AN: 3896

American (AMR) AF: 0.705 AC: 1764 AN: 2502

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 3443 AN: 5124

East Asian (EAS) AF: 0.791 AC: 9024 AN: 11408

South Asian (SAS) AF: 0.711 AC: 509 AN: 716

European-Finnish (FIN) AF: 0.725 AC: 319 AN: 440

Middle Eastern (MID) AF: 0.675 AC: 332 AN: 492

European-Non Finnish (NFE) AF: 0.719 AC: 35940 AN: 50018

Other (OTH) AF: 0.742 AC: 5027 AN: 6774

GnomAD4 genome AF: 0.783 AC: 119186 AN: 152262 Hom.: 47424 Cov.: 34 AF XY: 0.782 AC XY: 58242 AN XY: 74456

African (AFR) AF: 0.946 AC: 39312 AN: 41566

American (AMR) AF: 0.690 AC: 10562 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2289 AN: 3472

East Asian (EAS) AF: 0.775 AC: 4013 AN: 5180

South Asian (SAS) AF: 0.731 AC: 3529 AN: 4828

European-Finnish (FIN) AF: 0.739 AC: 7824 AN: 10594

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49212 AN: 68002

Other (OTH) AF: 0.758 AC: 1602 AN: 2114

Alfa AF: 0.742 Hom.: 24135

Bravo AF: 0.787

Asia WGS AF: 0.753 AC: 2620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.37
PhyloP100		-0.022
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs9529; hg19: chr6-41903007;