14-95191685-G-A

Position:

chr14-95191685-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024734.4(CLMN):c.2888C>T(p.Pro963Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,612,860 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0098 ( 23 hom., cov: 32)

Exomes 𝑓: 0.00095 ( 22 hom. )

Consequence

CLMN
NM_024734.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.00100

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025978386).

BP6

Variant 14-95191685-G-A is Benign according to our data. Variant chr14-95191685-G-A is described in ClinVar as [Benign]. Clinvar id is 786255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00985 (1499/152232) while in subpopulation AFR AF= 0.0345 (1434/41514). AF 95% confidence interval is 0.0331. There are 23 homozygotes in gnomad4. There are 686 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLMN	NM_024734.4 linkuse as main transcript	c.2888C>T	p.Pro963Leu	missense_variant	13/13	ENST00000298912.9	NP_079010.2	Q96JQ2Q6NUQ2
CLMN	XM_011537158.2 linkuse as main transcript	c.2981C>T	p.Pro994Leu	missense_variant	14/14		XP_011535460.1
CLMN	XM_017021646.2 linkuse as main transcript	c.2921C>T	p.Pro974Leu	missense_variant	14/14		XP_016877135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLMN	ENST00000298912.9 linkuse as main transcript	c.2888C>T	p.Pro963Leu	missense_variant	13/13	1	NM_024734.4	ENSP00000298912.3		Q96JQ2

Frequencies

GnomAD3 genomes

AF:

0.00984

AC:

1497

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0346

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00245

AC:

611

AN:

249504

Hom.:

AF XY:

0.00170

AC XY:

230

AN XY:

134976

show subpopulations

Gnomad AFR exome

AF:

0.0331

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000445

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.000952

AC:

1391

AN:

1460628

Hom.:

Cov.:

AF XY:

0.000762

AC XY:

554

AN XY:

726640

show subpopulations

Gnomad4 AFR exome

AF:

0.0341

Gnomad4 AMR exome

AF:

0.00190

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.00207

GnomAD4 genome

AF:

0.00985

AC:

1499

AN:

152232

Hom.:

Cov.:

AF XY:

0.00922

AC XY:

686

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0345

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.00163

Hom.:

Bravo

AF:

0.0109

ESP6500AA

AF:

0.0354

AC:

156

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00306

AC:

372

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.076

T;.

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.69

T;T

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-0.42

MutationAssessor

Benign

1.0

L;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.3

N;D

REVEL

Benign

0.19

Sift

Benign

0.23

T;T

Sift4G

Uncertain

0.019

D;D

Polyphen

0.032

B;.

Vest4

0.062

MVP

0.77

MPC

0.11

ClinPred

0.011

GERP RS

-0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.035

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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