Variant 14-95193905-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_024734.4(CLMN):c.2784T>C(p.Tyr928Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0987 in 1,613,348 control chromosomes in the GnomAD database, including 10,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.10 ( 1039 hom., cov: 32)

Exomes 𝑓: 0.098 ( 9501 hom. )

Consequence

CLMN
NM_024734.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.15

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 14-95193905-A-G is Benign according to our data. Variant chr14-95193905-A-G is described in ClinVar as [Benign]. Clinvar id is 3055637.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLMN	NM_024734.4 linkuse as main transcript	c.2784T>C	p.Tyr928Tyr	synonymous_variant	12/13	ENST00000298912.9	NP_079010.2	Q96JQ2Q6NUQ2
CLMN	XM_011537158.2 linkuse as main transcript	c.2784T>C	p.Tyr928Tyr	synonymous_variant	12/14		XP_011535460.1
CLMN	XM_017021646.2 linkuse as main transcript	c.2724T>C	p.Tyr908Tyr	synonymous_variant	12/14		XP_016877135.1
CLMN	XM_011537159.3 linkuse as main transcript	c.*54T>C		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.2784T>C	p.Tyr928Tyr	synonymous_variant	12/13	1	NM_024734.4	ENSP00000298912.3		Q96JQ2

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15784

AN:

152078

Hom.:

1037

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.0746

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0809

Gnomad OTH

AF:

0.106

GnomAD3 exomes

AF:

0.119

AC:

29775

AN:

250818

Hom.:

2630

AF XY:

0.123

AC XY:

16661

AN XY:

135532

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.0456

Gnomad ASJ exome

AF:

0.152

Gnomad EAS exome

AF:

0.372

Gnomad SAS exome

AF:

0.182

Gnomad FIN exome

AF:

0.125

Gnomad NFE exome

AF:

0.0815

Gnomad OTH exome

AF:

0.112

GnomAD4 exome

AF:

0.0982

AC:

143437

AN:

1461152

Hom.:

9501

Cov.:

AF XY:

0.101

AC XY:

73604

AN XY:

726828

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.0484

Gnomad4 ASJ exome

AF:

0.152

Gnomad4 EAS exome

AF:

0.382

Gnomad4 SAS exome

AF:

0.183

Gnomad4 FIN exome

AF:

0.121

Gnomad4 NFE exome

AF:

0.0800

Gnomad4 OTH exome

AF:

0.113

GnomAD4 genome

AF:

0.104

AC:

15808

AN:

152196

Hom.:

1039

Cov.:

AF XY:

0.110

AC XY:

8151

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.0750

Gnomad4 ASJ

AF:

0.149

Gnomad4 EAS

AF:

0.359

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.130

Gnomad4 NFE

AF:

0.0809

Gnomad4 OTH

AF:

0.104

Alfa

AF:

0.0875

Hom.:

867

Bravo

AF:

0.0990

Asia WGS

AF:

0.246

AC:

852

AN:

3478

EpiCase

AF:

0.0799

EpiControl

AF:

0.0887

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CLMN-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as 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

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.2

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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