Genetic Variant LSM7:p.Arg56Gln (chr19-2324127-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_016199.3(LSM7):c.167G>A(p.Arg56Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000121 in 1,565,440 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

LSM7
NM_016199.3 missense, splice_region

Scores

Splicing: ADA: 0.6698

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.70

Variant links:

Genes affected

LSM7 (HGNC:20470): (LSM7 homolog, U6 small nuclear RNA and mRNA degradation associated) Sm-like proteins were identified in a variety of organisms based on sequence homology with the Sm protein family (see SNRPD2; MIM 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, Apr 2004]

LSM7 links:

ENSG00000273734 (HGNC:):

ENSG00000273734 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSM7	NM_016199.3 link	c.167G>A	p.Arg56Gln	missense_variant, splice_region_variant	Exon 3 of 4	ENST00000252622.15	NP_057283.1	Q9UK45

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSM7	ENST00000252622.15 link	c.167G>A	p.Arg56Gln	missense_variant, splice_region_variant	Exon 3 of 4	1	NM_016199.3	ENSP00000252622.8		Q9UK45
ENSG00000273734	ENST00000621615.1 link	n.147-10475C>T		intron_variant	Intron 1 of 7	2		ENSP00000481965.1		A0A087WYN8

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151522

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

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:

0.00000551

AC:

AN:

181562

Hom.:

AF XY:

0.0000103

AC XY:

AN XY:

97180

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000372

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:

0.0000120

AC:

AN:

1413918

Hom.:

Cov.:

AF XY:

0.0000172

AC XY:

AN XY:

698980

show subpopulations

Gnomad4 AFR exome

AF:

0.0000310

Gnomad4 AMR exome

AF:

0.0000265

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:

0.0000138

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151522

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73922

show subpopulations

Gnomad4 AFR

AF:

0.0000243

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

Bravo

AF:

0.0000340

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.167G>A (p.R56Q) alteration is located in exon 3 (coding exon 3) of the LSM7 gene. This alteration results from a G to A substitution at nucleotide position 167, causing the arginine (R) at amino acid position 56 to be replaced by a glutamine (Q). 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

Pathogenic

0.91

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.61

D;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

D;D

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.54

D;D

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.8

M;.

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-3.6

D;.

REVEL

Benign

0.19

Sift

Uncertain

0.014

D;.

Sift4G

Uncertain

0.014

D;D

Polyphen

0.84

P;.

Vest4

0.53

MutPred

0.44

Loss of stability (P = 0.1096);.;

MVP

0.74

MPC

1.6

ClinPred

0.97

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.41

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.67

dbscSNV1_RF

Pathogenic

0.77

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