1-35743189-T-C

Variant names:

• chr1-35743189-T-C
• NM_022111.4:c.3095A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022111.4(CLSPN):​c.3095A>G​(p.Asp1032Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. D1032V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CLSPN NM_022111.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96

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]

ENSG00000232335 (HGNC:40896):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1691831).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLSPN	NM_022111.4	c.3095A>G	p.Asp1032Gly	missense_variant	Exon 18 of 25	ENST00000318121.8	NP_071394.2
CLSPN	NM_001330490.2	c.3095A>G	p.Asp1032Gly	missense_variant	Exon 18 of 25		NP_001317419.1
CLSPN	NM_001190481.2	c.2903A>G	p.Asp968Gly	missense_variant	Exon 17 of 24		NP_001177410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLSPN	ENST00000318121.8	c.3095A>G	p.Asp1032Gly	missense_variant	Exon 18 of 25	1	NM_022111.4	ENSP00000312995.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461838 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727222

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	.;T;.;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.64	T;T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.5	M;M;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.6	D;D;N;D
REVEL	Benign	0.11
Sift	Benign	0.049	D;D;T;D
Sift4G	Uncertain	0.026	D;D;D;D
Polyphen		0.99, 0.94	.;D;P;.
Vest4		0.17
MutPred		0.17		Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);.;.;
MVP		0.46
MPC		0.11
ClinPred		0.90	D
GERP RS		5.6
Varity_R		0.19
gMVP		0.023

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.

Other links and lift over

hg19: chr1-36208790;