Genetic Variant LSM3:c.21+136C>G (chr3-14179017-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014463.3(LSM3):c.21+136C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 934,176 control chromosomes in the GnomAD database, including 3,990 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 602 hom., cov: 33)

Exomes 𝑓: 0.058 ( 3388 hom. )

Consequence

LSM3
NM_014463.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.888

Variant links:

Genes affected

LSM3 (HGNC:17874): (LSM3 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]

LSM3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 3-14179017-C-G is Benign according to our data. Variant chr3-14179017-C-G is described in ClinVar as [Benign]. Clinvar id is 1283981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSM3	NM_014463.3 link	c.21+136C>G		intron_variant	Intron 1 of 3	ENST00000306024.4	NP_055278.1	P62310

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSM3	ENST00000306024.4 link	c.21+136C>G		intron_variant	Intron 1 of 3	1	NM_014463.3	ENSP00000302160.3		P62310

Frequencies

GnomAD3 genomes

AF:

0.0519

AC:

7902

AN:

152110

Hom.:

604

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00893

Gnomad AMI

AF:

0.0868

Gnomad AMR

AF:

0.0826

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.366

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0339

Gnomad OTH

AF:

0.0527

GnomAD4 exome

AF:

0.0576

AC:

45040

AN:

781948

Hom.:

3388

AF XY:

0.0585

AC XY:

23735

AN XY:

405400

show subpopulations

Gnomad4 AFR exome

AF:

0.00700

Gnomad4 AMR exome

AF:

0.102

Gnomad4 ASJ exome

AF:

0.0144

Gnomad4 EAS exome

AF:

0.342

Gnomad4 SAS exome

AF:

0.0923

Gnomad4 FIN exome

AF:

0.114

Gnomad4 NFE exome

AF:

0.0313

Gnomad4 OTH exome

AF:

0.0581

GnomAD4 genome

AF:

0.0520

AC:

7909

AN:

152228

Hom.:

602

Cov.:

AF XY:

0.0584

AC XY:

4343

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00891

Gnomad4 AMR

AF:

0.0832

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.365

Gnomad4 SAS

AF:

0.106

Gnomad4 FIN

AF:

0.124

Gnomad4 NFE

AF:

0.0339

Gnomad4 OTH

AF:

0.0536

Alfa

AF:

0.0208

Hom.:

Bravo

AF:

0.0480

Asia WGS

AF:

0.198

AC:

687

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 11, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

5.6

DANN

Benign

0.45

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