rs3731055

Positions:

• chr3-14178939-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014463.3(LSM3):​c.21+58C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,595,208 control chromosomes in the GnomAD database, including 1,596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (209 hom., cov: 33)
  • Exomes 𝑓: 0.016 (1387 hom.)
• Consequence: LSM3 NM_014463.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.03

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 3-14178939-C-T is Benign according to our data. Variant chr3-14178939-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1167092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LSM3	NM_014463.3	c.21+58C>T		intron_variant		ENST00000306024.4	NP_055278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LSM3	ENST00000306024.4	c.21+58C>T		intron_variant		1	NM_014463.3	ENSP00000302160	P1

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3393 AN: 152134 Hom.: 208 Cov.: 33

Gnomad AFR AF: 0.00589

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0918

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.0375

Gnomad FIN AF: 0.00829

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00441

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.0161 AC: 23195 AN: 1442956 Hom.: 1387 AF XY: 0.0160 AC XY: 11471 AN XY: 718972

Gnomad4 AFR exome AF: 0.00450

Gnomad4 AMR exome AF: 0.122

Gnomad4 ASJ exome AF: 0.00392

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.0300

Gnomad4 FIN exome AF: 0.0115

Gnomad4 NFE exome AF: 0.00404

Gnomad4 OTH exome AF: 0.0221

GnomAD4 genome AF: 0.0224 AC: 3406 AN: 152252 Hom.: 209 Cov.: 33 AF XY: 0.0256 AC XY: 1907 AN XY: 74452

Gnomad4 AFR AF: 0.00602

Gnomad4 AMR AF: 0.0918

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.0375

Gnomad4 FIN AF: 0.00829

Gnomad4 NFE AF: 0.00443

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0207 Hom.: 26

Bravo AF: 0.0294

Asia WGS AF: 0.117 AC: 409 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2019	This variant is associated with the following publications: (PMID: 21822670) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 18, 2023	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.9
DANN	Benign	0.75

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

Other links and lift over

dbSNP: rs3731055; hg19: chr3-14220439;