Genetic Variant LSM11:p.Arg6Leu (chr5-157743767-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_173491.4(LSM11):c.17G>T(p.Arg6Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00213 in 1,405,064 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R6W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.011 ( 32 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 28 hom. )

Consequence

LSM11
NM_173491.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.02

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

Aicardi-Goutieres syndrome 8
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
Tourette syndrome
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

LSM11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001960814).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0108 (1638/152166) while in subpopulation AFR AF = 0.038 (1577/41532). AF 95% confidence interval is 0.0364. There are 32 homozygotes in GnomAd4. There are 781 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 32 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSM11	NM_173491.4 link	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 4	ENST00000286307.6	NP_775762.1	P83369

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSM11	ENST00000286307.6 link	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 4	1	NM_173491.4	ENSP00000286307.5		P83369

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1636

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0380

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00813

GnomAD2 exomes

AF:

0.00137

AC:

AN:

40128

AF XY:

0.00101

show subpopulations

Gnomad AFR exome

AF:

0.0501

Gnomad AMR exome

AF:

0.00144

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00195

GnomAD4 exome

AF:

0.00109

AC:

1361

AN:

1252898

Hom.:

Cov.:

AF XY:

0.000989

AC XY:

607

AN XY:

613980

show subpopulations

African (AFR)

AF:

0.0429

AC:

1060

AN:

24720

American (AMR)

AF:

0.00149

AC:

AN:

16058

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18514

East Asian (EAS)

AF:

0.00

AC:

AN:

28570

South Asian (SAS)

AF:

0.000113

AC:

AN:

62084

European-Finnish (FIN)

AF:

0.0000288

AC:

AN:

34690

Middle Eastern (MID)

AF:

0.00137

AC:

AN:

3660

European-Non Finnish (NFE)

AF:

0.000133

AC:

135

AN:

1013580

Other (OTH)

AF:

0.00253

AC:

129

AN:

51022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

120

180

240

300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0108

AC:

1638

AN:

152166

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

781

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0380

AC:

1577

AN:

41532

American (AMR)

AF:

0.00196

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

67958

Other (OTH)

AF:

0.00804

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

164

246

328

410

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.0127

ExAC

AF:

0.00179

AC:

159

Asia WGS

AF:

0.00145

AC:

AN:

3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.014

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.065

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.53

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.90

PhyloP100

5.0

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.29

Sift

Benign

0.053

Sift4G

Uncertain

0.060

Polyphen

0.29

Vest4

0.33

MVP

0.48

MPC

1.1

ClinPred

0.055

GERP RS

3.1

PromoterAI

0.035

Neutral

(source)

Varity_R

0.25

gMVP

0.35

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over