3-157159899-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_020307.4(CCNL1):​c.196C>A​(p.Pro66Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,605,318 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000089 ( 1 hom. )

Consequence

CCNL1
NM_020307.4 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.030341566).
BS2
High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCNL1NM_020307.4 linkuse as main transcriptc.196C>A p.Pro66Thr missense_variant 1/11 ENST00000295926.8 NP_064703.1
CCNL1NM_001308185.2 linkuse as main transcriptc.196C>A p.Pro66Thr missense_variant 1/11 NP_001295114.1
CCNL1XM_006713710.5 linkuse as main transcriptc.196C>A p.Pro66Thr missense_variant 1/10 XP_006713773.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCNL1ENST00000295926.8 linkuse as main transcriptc.196C>A p.Pro66Thr missense_variant 1/111 NM_020307.4 ENSP00000295926 P1Q9UK58-1

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152192
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00124
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
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:
0.0000558
AC:
13
AN:
232904
Hom.:
1
AF XY:
0.0000396
AC XY:
5
AN XY:
126204
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000395
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000895
AC:
13
AN:
1453126
Hom.:
1
Cov.:
31
AF XY:
0.00000692
AC XY:
5
AN XY:
722024
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000299
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
152192
Hom.:
0
Cov.:
33
AF XY:
0.000188
AC XY:
14
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00124
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000982

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 GeneticsMar 18, 2024The c.196C>A (p.P66T) alteration is located in exon 1 (coding exon 1) of the CCNL1 gene. This alteration results from a C to A substitution at nucleotide position 196, causing the proline (P) at amino acid position 66 to be replaced by a threonine (T). 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
0.12
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
22
DANN
Benign
0.65
DEOGEN2
Benign
0.017
.;T;.
Eigen
Benign
-0.98
Eigen_PC
Benign
-0.87
FATHMM_MKL
Benign
0.75
D
LIST_S2
Uncertain
0.88
D;D;D
M_CAP
Uncertain
0.097
D
MetaRNN
Benign
0.030
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.19
N;N;N
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-1.0
N;N;N
REVEL
Benign
0.031
Sift
Benign
0.60
T;T;T
Sift4G
Benign
0.64
T;T;T
Polyphen
0.025
.;B;.
Vest4
0.095
MutPred
0.40
Gain of glycosylation at P66 (P = 0.0597);Gain of glycosylation at P66 (P = 0.0597);Gain of glycosylation at P66 (P = 0.0597);
MVP
0.34
MPC
1.4
ClinPred
0.079
T
GERP RS
1.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.16
gMVP
0.62

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: rs1166452024; hg19: chr3-156877688; API