Variant chr19-34209039-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015578.4(LSM14A):c.526C>G(p.Gln176Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,423,570 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27696842).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LSM14A	NM_015578.4 linkuse as main transcript	c.526C>G	p.Gln176Glu	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.526C>G	p.Gln176Glu	missense_variant	4/10	1	NM_015578.4	ENSP00000446271.2		Q8ND56-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000419

AC:

AN:

238616

Hom.:

AF XY:

0.00000776

AC XY:

AN XY:

128906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000323

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000140

AC:

AN:

1423570

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

706456

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000479

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

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

Jun 28, 2024

The c.526C>G (p.Q176E) alteration is located in exon 4 (coding exon 4) of the LSM14A gene. This alteration results from a C to G substitution at nucleotide position 526, causing the glutamine (Q) at amino acid position 176 to be replaced by a glutamic acid (E). 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

0.092

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.010

.;T;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.96

.;.;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.28

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;M;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.49

N;N;.

REVEL

Benign

0.12

Sift

Benign

0.048

D;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.77

P;P;.

Vest4

0.70

MutPred

0.38

Loss of MoRF binding (P = 0.0307);Loss of MoRF binding (P = 0.0307);.;

MVP

0.48

MPC

0.075

ClinPred

0.41

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.52

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