Variant 14-95202897-G-T 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_024734.4(CLMN):c.2452C>A(p.Pro818Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

CLMN
NM_024734.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.418

Variant links:

Genes affected

CLMN (HGNC:19972): (calmin) Predicted to enable actin filament binding activity. Predicted to be involved in negative regulation of cell population proliferation and nuclear migration. Predicted to act upstream of or within neuron projection development. Predicted to be integral component of membrane. Predicted to be part of meiotic nuclear membrane microtubule tethering complex. Predicted to be active in cytoplasm and nuclear outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

CLMN links:

CLMN (HGNC:):

CLMN 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=0.06466457).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLMN	NM_024734.4 linkuse as main transcript	c.2452C>A	p.Pro818Thr	missense_variant	9/13	ENST00000298912.9	NP_079010.2	Q96JQ2Q6NUQ2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLMN	ENST00000298912.9 linkuse as main transcript	c.2452C>A	p.Pro818Thr	missense_variant	9/13	1	NM_024734.4	ENSP00000298912.3		Q96JQ2
CLMN	ENST00000556454.1 linkuse as main transcript	n.1816C>A		non_coding_transcript_exon_variant	3/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.00e-7

AC:

AN:

1428138

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

708910

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

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

Nov 28, 2024

The c.2452C>A (p.P818T) alteration is located in exon 9 (coding exon 9) of the CLMN gene. This alteration results from a C to A substitution at nucleotide position 2452, causing the proline (P) at amino acid position 818 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

0.077

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

0.52

DANN

Benign

0.78

DEOGEN2

Benign

0.031

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.59

M_CAP

Benign

0.059

MetaRNN

Benign

0.065

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.33

REVEL

Benign

0.15

Sift

Benign

0.37

Sift4G

Benign

0.13

Polyphen

0.091

Vest4

0.071

MutPred

0.078

Gain of phosphorylation at P818 (P = 0.0101);

MVP

0.73

MPC

0.12

ClinPred

0.040

GERP RS

-2.4

Varity_R

0.026

gMVP

0.11

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