Variant 5-157743958-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_173491.4(LSM11):c.208G>A(p.Gly70Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00199 in 1,324,358 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 7 hom. )

Consequence

LSM11
NM_173491.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.184

Variant links:

Genes affected

LSM11 (HGNC:30860): (LSM11, U7 small nuclear RNA associated) Enables U7 snRNA binding activity. Involved in positive regulation of G1/S transition of mitotic cell cycle. Located in nuclear body. Part of U7 snRNP and telomerase holoenzyme complex. Implicated in Aicardi-Goutieres syndrome. [provided by Alliance of Genome Resources, Apr 2022]

LSM11 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=0.0071845055).

BP6

Variant 5-157743958-G-A is Benign according to our data. Variant chr5-157743958-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3037709.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LSM11	NM_173491.4 linkuse as main transcript	c.208G>A	p.Gly70Ser	missense_variant	1/4	ENST00000286307.6	NP_775762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LSM11	ENST00000286307.6 linkuse as main transcript	c.208G>A	p.Gly70Ser	missense_variant	1/4	1	NM_173491.4	ENSP00000286307	P1

Frequencies

GnomAD3 genomes

AF:

0.00165

AC:

248

AN:

150418

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00212

Gnomad ASJ

AF:

0.000290

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.000400

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00270

Gnomad OTH

AF:

0.00195

GnomAD3 exomes

AF:

0.00290

AC:

171

AN:

59040

Hom.:

AF XY:

0.00281

AC XY:

AN XY:

35220

show subpopulations

Gnomad AFR exome

AF:

0.000505

Gnomad AMR exome

AF:

0.00318

Gnomad ASJ exome

AF:

0.000372

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00229

Gnomad FIN exome

AF:

0.00160

Gnomad NFE exome

AF:

0.00405

Gnomad OTH exome

AF:

0.00152

GnomAD4 exome

AF:

0.00204

AC:

2391

AN:

1173834

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

1178

AN XY:

569362

show subpopulations

Gnomad4 AFR exome

AF:

0.000244

Gnomad4 AMR exome

AF:

0.00237

Gnomad4 ASJ exome

AF:

0.000175

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00160

Gnomad4 FIN exome

AF:

0.00104

Gnomad4 NFE exome

AF:

0.00224

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.00165

AC:

248

AN:

150524

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

110

AN XY:

73492

show subpopulations

Gnomad4 AFR

AF:

0.000484

Gnomad4 AMR

AF:

0.00211

Gnomad4 ASJ

AF:

0.000290

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.000400

Gnomad4 NFE

AF:

0.00270

Gnomad4 OTH

AF:

0.00192

Alfa

AF:

0.00277

Hom.:

Bravo

AF:

0.00161

ExAC

AF:

0.00161

AC:

168

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LSM11-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 23, 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

0.11

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.012

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.57

M_CAP

Benign

0.072

MetaRNN

Benign

0.0072

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.83

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.45

REVEL

Benign

0.022

Sift

Benign

0.22

Sift4G

Benign

0.47

Polyphen

0.36

Vest4

0.23

MVP

0.15

MPC

0.95

ClinPred

0.011

GERP RS

1.5

Varity_R

0.047

gMVP

0.39

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