Genetic Variant LSM14A:p.Thr459Ile (chr19-34226415-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001114093.3(LSM14A):c.1376C>T(p.Thr459Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000505 in 1,387,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0000040 ( 0 hom. )

Consequence

LSM14A
NM_001114093.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.65

Publications

0 publications found

Variant links:

Genes affected

LSM14A (HGNC:24489): (LSM14A mRNA processing body assembly factor) Sm-like proteins were identified in a variety of organisms based on sequence homology with the Sm protein family (see SNRPD2; 601061). Sm-like proteins contain the Sm sequence motif, which consists of 2 regions separated by a linker of variable length that folds as a loop. The Sm-like proteins are thought to form a stable heteromer present in tri-snRNP particles, which are important for pre-mRNA splicing.[supplied by OMIM, Mar 2008]

LSM14A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26208472).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114093.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LSM14A	NM_015578.4	MANE Select	c.1369-950C>T		intron	N/A	NP_056393.2	Q8ND56-2
LSM14A	NM_001114093.3		c.1376C>T	p.Thr459Ile	missense	Exon 10 of 11	NP_001107565.1	Q8ND56-1
LSM14A	NM_001384423.1		c.1253C>T	p.Thr418Ile	missense	Exon 9 of 10	NP_001371352.1	Q8ND56-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LSM14A	ENST00000433627.9	TSL:1	c.1376C>T	p.Thr459Ile	missense	Exon 10 of 11	ENSP00000413964.3	Q8ND56-1
LSM14A	ENST00000544216.8	TSL:1 MANE Select	c.1369-950C>T		intron	N/A	ENSP00000446271.2	Q8ND56-2
LSM14A	ENST00000540746.6	TSL:2	c.1253C>T	p.Thr418Ile	missense	Exon 9 of 10	ENSP00000446451.1	Q8ND56-3

Frequencies

GnomAD3 genomes

AF:

0.0000144

AC:

AN:

138510

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:

0.0000308

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

100710

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000400

AC:

AN:

1248810

Hom.:

Cov.:

AF XY:

0.00000648

AC XY:

AN XY:

617700

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26120

American (AMR)

AF:

0.00

AC:

AN:

25276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22870

East Asian (EAS)

AF:

0.00

AC:

AN:

32068

South Asian (SAS)

AF:

0.00

AC:

AN:

67704

European-Finnish (FIN)

AF:

0.0000260

AC:

AN:

38418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5066

European-Non Finnish (NFE)

AF:

0.00000306

AC:

AN:

979220

Other (OTH)

AF:

0.0000192

AC:

AN:

52068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

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:

0.0000144

AC:

AN:

138510

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

66138

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

37398

American (AMR)

AF:

0.00

AC:

AN:

13068

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3404

East Asian (EAS)

AF:

0.00

AC:

AN:

4804

South Asian (SAS)

AF:

0.00

AC:

AN:

4454

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

260

European-Non Finnish (NFE)

AF:

0.0000308

AC:

AN:

64952

Other (OTH)

AF:

0.00

AC:

AN:

1878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

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:

0.00

Hom.:

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

Uncertain

0.35

BayesDel_addAF

Uncertain

0.064

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.54

M_CAP

Benign

0.0091

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

2.7

PROVEAN

Benign

-1.2

REVEL

Benign

0.17

Sift

Pathogenic

0.0

Sift4G

Benign

0.12

Polyphen

0.99

Vest4

0.47

MutPred

0.18

Loss of phosphorylation at T459 (P = 0.0112)

MVP

0.27

ClinPred

0.65

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.36

Mutation Taster

=80/20

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over