chr3-157148386-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_020307.4(CCNL1):​c.1436G>A​(p.Arg479Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000867 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

CCNL1
NM_020307.4 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.00
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.35951844).
BS2
High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCNL1NM_020307.4 linkuse as main transcriptc.1436G>A p.Arg479Gln missense_variant 11/11 ENST00000295926.8 NP_064703.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCNL1ENST00000295926.8 linkuse as main transcriptc.1436G>A p.Arg479Gln missense_variant 11/111 NM_020307.4 ENSP00000295926 P1Q9UK58-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152160
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251446
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135896
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000752
AC:
11
AN:
1461888
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000894
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152160
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsFeb 28, 2023The c.1436G>A (p.R479Q) alteration is located in exon 11 (coding exon 11) of the CCNL1 gene. This alteration results from a G to A substitution at nucleotide position 1436, causing the arginine (R) at amino acid position 479 to be replaced by a glutamine (Q). 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
Benign
0.15
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.26
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.053
T
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.36
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.4
M
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.11
Sift
Uncertain
0.028
D
Sift4G
Benign
0.11
T
Polyphen
1.0
D
Vest4
0.45
MVP
0.44
MPC
0.58
ClinPred
0.81
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.40
gMVP
0.46

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.

Other links and lift over

dbSNP: rs762041871; hg19: chr3-156866175; API