Variant 3-157160058-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020307.4(CCNL1):c.37G>T(p.Ala13Ser) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCNL1
NM_020307.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.163

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060730696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCNL1	NM_020307.4 linkuse as main transcript	c.37G>T	p.Ala13Ser	missense_variant	1/11	ENST00000295926.8	NP_064703.1
CCNL1	NM_001308185.2 linkuse as main transcript	c.37G>T	p.Ala13Ser	missense_variant	1/11		NP_001295114.1
CCNL1	XM_006713710.5 linkuse as main transcript	c.37G>T	p.Ala13Ser	missense_variant	1/10		XP_006713773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNL1	ENST00000295926.8 linkuse as main transcript	c.37G>T	p.Ala13Ser	missense_variant	1/11	1	NM_020307.4	ENSP00000295926	P1	Q9UK58-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1407096

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

694958

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 08, 2024

The c.37G>T (p.A13S) alteration is located in exon 1 (coding exon 1) of the CCNL1 gene. This alteration results from a G to T substitution at nucleotide position 37, causing the alanine (A) at amino acid position 13 to be replaced by a serine (S). 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

0.093

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.015

.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.061

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.12

N;N;N

REVEL

Benign

0.017

Sift

Benign

0.081

T;T;T

Sift4G

Benign

0.35

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.14

MutPred

0.35

Gain of glycosylation at A13 (P = 0.0011);Gain of glycosylation at A13 (P = 0.0011);Gain of glycosylation at A13 (P = 0.0011);

MVP

0.63

MPC

1.1

ClinPred

0.083

GERP RS

-0.24

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.058

gMVP

0.21

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over