Genetic Variant NM_173491.4:c.29C>G (chr5-157743779-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_173491.4(LSM11):c.29C>G(p.Ser10Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000896 in 1,418,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000091 ( 0 hom. )

Consequence

LSM11
NM_173491.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.792

Publications

1 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02171591).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173491.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSM11	NM_173491.4	MANE Select	c.29C>G	p.Ser10Trp	missense	Exon 1 of 4	NP_775762.1	P83369

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSM11	ENST00000286307.6	TSL:1 MANE Select	c.29C>G	p.Ser10Trp	missense	Exon 1 of 4	ENSP00000286307.5	P83369

Frequencies

GnomAD3 genomes

AF:

0.0000790

AC:

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000205

AC:

AN:

48704

AF XY:

0.000174

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000284

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000362

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000908

AC:

115

AN:

1266030

Hom.:

Cov.:

AF XY:

0.0000885

AC XY:

AN XY:

621438

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25038

American (AMR)

AF:

0.000292

AC:

AN:

17140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19072

East Asian (EAS)

AF:

0.00

AC:

AN:

28818

South Asian (SAS)

AF:

0.0000626

AC:

AN:

63890

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36346

Middle Eastern (MID)

AF:

0.000261

AC:

AN:

3836

European-Non Finnish (NFE)

AF:

0.000101

AC:

103

AN:

1020278

Other (OTH)

AF:

0.0000388

AC:

AN:

51612

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000789

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41520

American (AMR)

AF:

0.0000654

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.000414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

67922

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000474

Hom.:

Bravo

AF:

0.000102

ExAC

AF:

0.000129

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

Eigen

Benign

0.10

Eigen_PC

Benign

-0.0048

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.67

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.90

PhyloP100

0.79

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-2.0

REVEL

Benign

0.063

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.010

Polyphen

0.99

Vest4

0.36

MutPred

0.26

Loss of phosphorylation at S10 (P = 0.0017)

MVP

0.49

MPC

1.6

ClinPred

0.15

GERP RS

3.1

PromoterAI

-0.20

Neutral

(source)

Varity_R

0.27

gMVP

0.49

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over