chr3-157149576-C-T

Variant names:

• chr3-157149576-C-T
• rs144463229
• NM_020307.4:c.1042G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_020307.4(CCNL1):​c.1042G>A​(p.Ala348Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000899 in 1,613,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000094 (0 hom.)
• Consequence: CCNL1 NM_020307.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0360
• Publications: 3 publications found

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]

LINC00881 (HGNC:48567): (long intergenic non-protein coding RNA 881)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.021762788).
• BS2: High AC in GnomAd4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020307.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNL1	NM_020307.4	MANE Select	c.1042G>A	p.Ala348Thr	missense	Exon 9 of 11	NP_064703.1	Q9UK58-1
	CCNL1	NM_001308185.2		c.1042G>A	p.Ala348Thr	missense	Exon 9 of 11	NP_001295114.1	Q9UK58-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNL1	ENST00000295926.8	TSL:1 MANE Select	c.1042G>A	p.Ala348Thr	missense	Exon 9 of 11	ENSP00000295926.4	Q9UK58-1
	CCNL1	ENST00000464316.5	TSL:1	n.2858G>A		non_coding_transcript_exon	Exon 5 of 7
	CCNL1	ENST00000470121.5	TSL:1	n.*651G>A		non_coding_transcript_exon	Exon 11 of 13	ENSP00000417237.1	Q9UK58-4

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152154 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000997 AC: 25 AN: 250630 AF XY: 0.0000886

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.0000871

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000937 AC: 137 AN: 1461374 Hom.: 0 Cov.: 31 AF XY: 0.0000922 AC XY: 67 AN XY: 727028

African (AFR) AF: 0.0000299 AC: 1 AN: 33434

American (AMR) AF: 0.0000896 AC: 4 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39682

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.000105 AC: 117 AN: 1111780

Other (OTH) AF: 0.000132 AC: 8 AN: 60382

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152272 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74470

African (AFR) AF: 0.0000481 AC: 2 AN: 41554

American (AMR) AF: 0.0000654 AC: 1 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000114 Hom.: 0

Bravo AF: 0.0000718

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000988 AC: 12

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.89
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.60	N
PhyloP100		-0.036
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.083
Sift	Benign	0.85	T
Sift4G	Benign	0.69	T
Polyphen		0.0020	B
Vest4		0.024
MVP		0.10
MPC		0.48
ClinPred		0.061	T
GERP RS		0.60
Varity_R		0.061
gMVP		0.18
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs144463229; hg19: chr3-156867365;