Genetic Variant NM_173491.4:c.50C>G (chr5-157743800-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173491.4(LSM11):c.50C>G(p.Ala17Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000066 in 1,317,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

LSM11
NM_173491.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.198

Publications

0 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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044262916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSM11	NM_173491.4 link	c.50C>G	p.Ala17Gly	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.50C>G	p.Ala17Gly	missense_variant	Exon 1 of 4	1	NM_173491.4	ENSP00000286307.5		P83369

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000107

AC:

AN:

93182

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000660

AC:

AN:

1317428

Hom.:

Cov.:

AF XY:

0.0000615

AC XY:

AN XY:

650160

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26350

American (AMR)

AF:

0.00

AC:

AN:

22764

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21126

East Asian (EAS)

AF:

0.00

AC:

AN:

30578

South Asian (SAS)

AF:

0.00

AC:

AN:

70610

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40682

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4338

European-Non Finnish (NFE)

AF:

0.0000831

AC:

AN:

1046984

Other (OTH)

AF:

0.00

AC:

AN:

53996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000889

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 18, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.50C>G (p.A17G) alteration is located in exon 1 (coding exon 1) of the LSM11 gene. This alteration results from a C to G substitution at nucleotide position 50, causing the alanine (A) at amino acid position 17 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0096

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.42

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.044

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

0.20

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.40

REVEL

Benign

0.035

Sift

Benign

0.15

Sift4G

Benign

0.31

Polyphen

0.0

Vest4

0.076

MutPred

0.096

Gain of methylation at R18 (P = 0.0717);

MVP

0.095

MPC

0.94

ClinPred

0.022

GERP RS

-0.55

PromoterAI

0.028

Neutral

(source)

Varity_R

0.058

gMVP

0.26

Mutation Taster

=91/9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over