14-54408796-A-T

Variant names:

• chr14-54408796-A-T
• rs2179896
• NM_005192.4:c.193+7A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005192.4(CDKN3):​c.193+7A>T variant causes a splice region, intron 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. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDKN3 NM_005192.4 splice_region, intron
• Scores: Splicing: ADA: 0.00003857
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49
• Publications: 15 publications found

Genes affected

CDKN3 (HGNC:1791): (cyclin dependent kinase inhibitor 3) The protein encoded by this gene belongs to the dual specificity protein phosphatase family. It was identified as a cyclin-dependent kinase inhibitor, and has been shown to interact with, and dephosphorylate CDK2 kinase, thus prevent the activation of CDK2 kinase. This gene was reported to be deleted, mutated, or overexpressed in several kinds of cancers. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN3	NM_005192.4	c.193+7A>T		splice_region_variant, intron_variant	Intron 4 of 7	ENST00000335183.11	NP_005183.2
CDKN3	NM_001330173.2	c.193+7A>T		splice_region_variant, intron_variant	Intron 4 of 8		NP_001317102.1
CDKN3	NM_001130851.2	c.73+7A>T		splice_region_variant, intron_variant	Intron 3 of 6		NP_001124323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN3	ENST00000335183.11	c.193+7A>T		splice_region_variant, intron_variant	Intron 4 of 7	1	NM_005192.4	ENSP00000335357.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1419114 Hom.: 0 Cov.: 43 AF XY: 0.00 AC XY: 0 AN XY: 704502

African (AFR) AF: 0.00 AC: 0 AN: 30956

American (AMR) AF: 0.00 AC: 0 AN: 35406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25128

East Asian (EAS) AF: 0.00 AC: 0 AN: 38054

South Asian (SAS) AF: 0.00 AC: 0 AN: 76126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5616

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096298

Other (OTH) AF: 0.00 AC: 0 AN: 58590

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 27984

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.022
DANN	Benign	0.45
PhyloP100		-2.5
PromoterAI		0.0076	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000039
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.090		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: rs2179896; hg19: chr14-54875514;