CLSPN p.Phe1239Leu

Variant names:

• chr1-35737369-A-T
• NM_022111.4:c.3717T>A
• CLSPN p.Phe1239Leu

Your query was ambiguous. Multiple possible variants found:

• chr1-35737369-A-T
• chr1-35737369-A-C
• chr1-35737371-A-G
• chr1-35737369-AAA-GAG
• chr1-35737369-AAA-TAG
• chr1-35737369-AAA-CAG

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022111.4(CLSPN):​c.3717T>A​(p.Phe1239Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F1239C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLSPN NM_022111.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.46
• Publications: 0 publications found

Genes affected

CLSPN (HGNC:19715): (claspin) The product of this gene is an essential upstream regulator of checkpoint kinase 1 and triggers a checkpoint arrest of the cell cycle in response to replicative stress or DNA damage. The protein is also required for efficient DNA replication during a normal S phase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42358506).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022111.4. 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
	CLSPN	NM_022111.4	MANE Select	c.3717T>A	p.Phe1239Leu	missense	Exon 23 of 25	NP_071394.2
	CLSPN	NM_001330490.2		c.3717T>A	p.Phe1239Leu	missense	Exon 23 of 25	NP_001317419.1	Q9HAW4-3
	CLSPN	NM_001190481.2		c.3525T>A	p.Phe1175Leu	missense	Exon 22 of 24	NP_001177410.1	Q9HAW4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLSPN	ENST00000318121.8	TSL:1 MANE Select	c.3717T>A	p.Phe1239Leu	missense	Exon 23 of 25	ENSP00000312995.3	Q9HAW4-1
	CLSPN	ENST00000251195.9	TSL:1	c.3717T>A	p.Phe1239Leu	missense	Exon 23 of 25	ENSP00000251195.5	Q9HAW4-3
	CLSPN	ENST00000520551.1	TSL:1	c.3558T>A	p.Phe1186Leu	missense	Exon 23 of 25	ENSP00000428848.1	E7ESG2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.075	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		3.5
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.13
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.039	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.34
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-36202970;