Variant 19-34208995-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_015578.4(LSM14A):c.482C>T(p.Ala161Val) variant causes a missense change. The variant allele was found at a frequency of 0.000031 in 1,611,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

LSM14A
NM_015578.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.72

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=0.11031744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LSM14A	NM_015578.4 linkuse as main transcript	c.482C>T	p.Ala161Val	missense_variant	4/10	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.482C>T	p.Ala161Val	missense_variant	4/10	1	NM_015578.4	ENSP00000446271.2		Q8ND56-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

250940

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135648

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000329

AC:

AN:

1458768

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

725688

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000741

AC:

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

Oct 09, 2024

The c.482C>T (p.A161V) alteration is located in exon 4 (coding exon 4) of the LSM14A gene. This alteration results from a C to T substitution at nucleotide position 482, causing the alanine (A) at amino acid position 161 to be replaced by a valine (V). 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

0.077

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

.;T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

0.040

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.77

.;.;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;M;.

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.3

N;N;.

REVEL

Benign

0.085

Sift

Benign

0.090

T;T;.

Sift4G

Benign

0.069

T;T;T

Polyphen

0.0070

B;B;.

Vest4

0.57

MutPred

0.18

Gain of loop (P = 0.024);Gain of loop (P = 0.024);.;

MVP

0.40

MPC

0.061

ClinPred

0.16

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.061

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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