Variant 14-95193906-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_024734.4(CLMN):c.2783A>G(p.Tyr928Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00391 in 1,613,880 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 12 hom. )

Consequence

CLMN
NM_024734.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.422

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02445978).

BP6

Variant 14-95193906-T-C is Benign according to our data. Variant chr14-95193906-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3044504.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLMN	NM_024734.4 linkuse as main transcript	c.2783A>G	p.Tyr928Cys	missense_variant	12/13	ENST00000298912.9	NP_079010.2	Q96JQ2Q6NUQ2
CLMN	XM_011537158.2 linkuse as main transcript	c.2783A>G	p.Tyr928Cys	missense_variant	12/14		XP_011535460.1
CLMN	XM_017021646.2 linkuse as main transcript	c.2723A>G	p.Tyr908Cys	missense_variant	12/14		XP_016877135.1
CLMN	XM_011537159.3 linkuse as main transcript	c.*53A>G		downstream_gene_variant			XP_011535461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLMN	ENST00000298912.9 linkuse as main transcript	c.2783A>G	p.Tyr928Cys	missense_variant	12/13	1	NM_024734.4	ENSP00000298912.3		Q96JQ2

Frequencies

GnomAD3 genomes

AF:

0.00226

AC:

344

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00393

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00191

AC:

481

AN:

251232

Hom.:

AF XY:

0.00199

AC XY:

270

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00183

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000360

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00329

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00408

AC:

5967

AN:

1461678

Hom.:

Cov.:

AF XY:

0.00389

AC XY:

2831

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.00172

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000476

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.00498

Gnomad4 OTH exome

AF:

0.00452

GnomAD4 genome

AF:

0.00226

AC:

344

AN:

152202

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

139

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00393

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00348

Hom.:

Bravo

AF:

0.00250

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00523

AC:

ExAC

AF:

0.00175

AC:

212

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00273

EpiControl

AF:

0.00285

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CLMN-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 15, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.085

Eigen

Benign

-0.025

Eigen_PC

Benign

-0.039

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.76

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.024

MetaSVM

Uncertain

0.030

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.49

Sift

Uncertain

0.0040

Sift4G

Benign

0.16

Polyphen

0.98

Vest4

0.41

MVP

0.95

MPC

0.42

ClinPred

0.021

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.19

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over