chr9-127785950-C-T

Variant names:

• chr9-127785950-C-T
• rs794728003
• ENST00000421939.5:c.153C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The ENST00000421939.5(CDK9):​c.153C>T​(p.Leu51Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L51L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDK9 ENST00000421939.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 0 publications found

Genes affected

CDK9 (HGNC:1780): (cyclin dependent kinase 9) The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK family members are highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2, and known as important cell cycle regulators. This kinase was found to be a component of the multiprotein complex TAK/P-TEFb, which is an elongation factor for RNA polymerase II-directed transcription and functions by phosphorylating the C-terminal domain of the largest subunit of RNA polymerase II. This protein forms a complex with and is regulated by its regulatory subunit cyclin T or cyclin K. HIV-1 Tat protein was found to interact with this protein and cyclin T, which suggested a possible involvement of this protein in AIDS. [provided by RefSeq, Jul 2008]

MIR2861 (HGNC:38221): (microRNA 2861) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of target mRNAs. This microRNA may play a role in osteoblast differentiation and a mutation in this gene is associated with osteoporosis. Altered expression of this microRNA has been observed in human cancers, with reduced expression seen in cervical cancer, while expression in papillary thyroid carcinoma (PTC) is increased. [provided by RefSeq, Mar 2017]

MIR3960 (HGNC:41595): (microRNA 3960) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=0.16 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000421939.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR2861	NR_036055.1		n.33C>T		non_coding_transcript_exon	Exon 1 of 1
	CDK9	NM_001261.4	MANE Select	c.-199C>T		upstream_gene	N/A	NP_001252.1
	MIR3960	NR_039767.1		n.*27C>T		downstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK9	ENST00000421939.5	TSL:3	c.153C>T	p.Leu51Leu	synonymous	Exon 1 of 3	ENSP00000395872.1
	MIR2861	ENST00000636310.1	TSL:6	n.33C>T		non_coding_transcript_exon	Exon 1 of 1
	CDK9	ENST00000373264.5	TSL:1 MANE Select	c.-199C>T		upstream_gene	N/A	ENSP00000362361.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 2

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Benign	0.95
PhyloP100		0.16
PromoterAI		0.013	Neutral

Splicing

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

Other links and lift over

dbSNP: rs794728003; hg19: chr9-130548229;