Genetic Variant LST1:p.Arg36Gly (chr6-31587727-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_ModerateBP6_Moderate

The NM_205839.3(LST1):c.106C>G(p.Arg36Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000751 in 1,597,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

LST1
NM_205839.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.153

Publications

0 publications found

Variant links:

Genes affected

LST1 (HGNC:14189): (leukocyte specific transcript 1) The protein encoded by this gene is a membrane protein that can inhibit the proliferation of lymphocytes. Expression of this gene is enhanced by lipopolysaccharide, interferon-gamma, and bacteria. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

LST1 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=0.20894247).

BP6

Variant 6-31587727-C-G is Benign according to our data. Variant chr6-31587727-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3868895.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205839.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LST1	NM_205839.3	MANE Select	c.106C>G	p.Arg36Gly	missense	Exon 3 of 5	NP_995311.2	O00453-1
LST1	NM_007161.3		c.106C>G	p.Arg36Gly	missense	Exon 2 of 4	NP_009092.3	O00453-11
LST1	NM_205837.3		c.106C>G	p.Arg36Gly	missense	Exon 3 of 4	NP_995309.2	O00453-12

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LST1	ENST00000438075.7	TSL:1 MANE Select	c.106C>G	p.Arg36Gly	missense	Exon 3 of 5	ENSP00000391929.3	O00453-1
LST1	ENST00000376093.6	TSL:1	c.106C>G	p.Arg36Gly	missense	Exon 2 of 4	ENSP00000365261.2	O00453-11
LST1	ENST00000339530.8	TSL:1	c.106C>G	p.Arg36Gly	missense	Exon 3 of 4	ENSP00000339201.4	O00453-12

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000913

AC:

AN:

219000

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:

0.0000207

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000692

AC:

AN:

1445214

Hom.:

Cov.:

AF XY:

0.00000836

AC XY:

AN XY:

717488

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33248

American (AMR)

AF:

0.00

AC:

AN:

42840

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25598

East Asian (EAS)

AF:

0.00

AC:

AN:

39280

South Asian (SAS)

AF:

0.00

AC:

AN:

83802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51772

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4516

European-Non Finnish (NFE)

AF:

0.00000905

AC:

AN:

1104604

Other (OTH)

AF:

0.00

AC:

AN:

59554

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.0000131

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41420

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Likely benign

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

-0.066

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.017

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.50

M_CAP

Benign

0.0087

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.98

PhyloP100

-0.15

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.10

Sift

Benign

0.075

Sift4G

Benign

0.13

Vest4

0.25

MutPred

0.37

Loss of solvent accessibility (P = 0.0044)

MVP

0.26

MPC

0.015

ClinPred

0.86

GERP RS

-1.5

PromoterAI

0.0074

Neutral

(source)

Varity_R

0.15

gMVP

0.046

Mutation Taster

=151/49

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over