Variant 3-157159833-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020307.4(CCNL1):c.262G>A(p.Glu88Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000215 in 1,396,826 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CCNL1
NM_020307.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.92

Variant links:

Genes affected

CCNL1 (HGNC:20569): (cyclin L1) Predicted to enable cyclin-dependent protein serine/threonine kinase regulator activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CCNL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNL1	NM_020307.4 link	c.262G>A	p.Glu88Lys	missense_variant	1/11	ENST00000295926.8	NP_064703.1	Q9UK58-1
CCNL1	NM_001308185.2 link	c.262G>A	p.Glu88Lys	missense_variant	1/11		NP_001295114.1	Q9UK58-6
CCNL1	XM_006713710.5 link	c.262G>A	p.Glu88Lys	missense_variant	1/10		XP_006713773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNL1	ENST00000295926.8 link	c.262G>A	p.Glu88Lys	missense_variant	1/11	1	NM_020307.4	ENSP00000295926.4		Q9UK58-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

164868

Hom.:

AF XY:

0.0000227

AC XY:

AN XY:

88274

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000303

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1396826

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

687466

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000279

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000659

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 25, 2024

The c.262G>A (p.E88K) alteration is located in exon 1 (coding exon 1) of the CCNL1 gene. This alteration results from a G to A substitution at nucleotide position 262, causing the glutamic acid (E) at amino acid position 88 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.094

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.13

.;T;.

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Uncertain

0.22

MetaRNN

Uncertain

0.67

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L;L

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Uncertain

0.40

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.050

T;T;T

Polyphen

1.0

.;D;.

Vest4

0.64

MutPred

0.57

Gain of methylation at E88 (P = 0.0028);Gain of methylation at E88 (P = 0.0028);Gain of methylation at E88 (P = 0.0028);

MVP

0.69

MPC

1.5

ClinPred

0.98

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.85

gMVP

0.91

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over