Variant 19-18309686-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000593829.6(LSM4):c.320C>G(p.Ala107Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,452,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LSM4
ENST00000593829.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.08

Variant links:

Genes affected

LSM4 (HGNC:17259): (LSM4 homolog, U6 small nuclear RNA and mRNA degradation associated) This gene encodes a member of the LSm family of RNA-binding proteins. LSm proteins form stable heteromers that bind specifically to the 3'-terminal oligo(U) tract of U6 snRNA and may play a role in pre-mRNA splicing by mediating U4/U6 snRNP formation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

LSM4 links:

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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=0.16193944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LSM4	NM_012321.5 linkuse as main transcript	c.320C>G	p.Ala107Gly	missense_variant	4/5	ENST00000593829.6	NP_036453.1	Q9Y4Z0
LSM4	NM_001252129.2 linkuse as main transcript	c.278C>G	p.Ala93Gly	missense_variant	3/4		NP_001239058.1	U3KQK1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LSM4	ENST00000593829.6 linkuse as main transcript	c.320C>G	p.Ala107Gly	missense_variant	4/5	1	NM_012321.5	ENSP00000469468.2		Q9Y4Z0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1452482

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722584

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 26, 2023

The c.320C>G (p.A107G) alteration is located in exon 4 (coding exon 4) of the LSM4 gene. This alteration results from a C to G substitution at nucleotide position 320, causing the alanine (A) at amino acid position 107 to be replaced by a glycine (G). 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

0.061

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

T;T;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.56

REVEL

Benign

0.14

Sift4G

Benign

0.66

T;T;.

Polyphen

0.052

B;.;.

Vest4

0.28

MutPred

0.35

Gain of relative solvent accessibility (P = 0.0082);.;Gain of relative solvent accessibility (P = 0.0082);

MVP

0.33

MPC

1.1

ClinPred

0.44

GERP RS

3.3

Varity_R

0.041

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over