Variant 19-34226415-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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

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:

LSM14A (HGNC:):

LSM14A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LSM14A	NM_015578.4 linkuse as main transcript	c.1369-950C>T		intron_variant		ENST00000544216.8	NP_056393.2	Q8ND56-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LSM14A	ENST00000544216.8 linkuse as main transcript	c.1369-950C>T		intron_variant		1	NM_015578.4	ENSP00000446271.2		Q8ND56-2

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

GnomAD4 exome

AF:

0.00000400

AC:

AN:

1248810

Hom.:

Cov.:

AF XY:

0.00000648

AC XY:

AN XY:

617700

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000260

Gnomad4 NFE exome

AF:

0.00000306

Gnomad4 OTH exome

AF:

0.0000192

GnomAD4 genome

AF:

0.0000144

AC:

AN:

138510

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

66138

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000308

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 14, 2024

The c.1376C>T (p.T459I) alteration is located in exon 10 (coding exon 10) of the LSM14A gene. This alteration results from a C to T substitution at nucleotide position 1376, causing the threonine (T) at amino acid position 459 to be replaced by an isoleucine (I). 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

Uncertain

0.35

BayesDel_addAF

Uncertain

0.064

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

.;T

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.54

T;.

M_CAP

Benign

0.0091

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

.;L

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.17

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.12

T;T

Polyphen

0.99

.;D

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over