dbSNP rs3731055: LSM3:c.21+58C>T (chr3-14178939-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.03

Publications

20 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
LSM3	NM_014463.3 link	c.21+58C>T		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+58C>T		intron_variant	Intron 1 of 3	1	NM_014463.3	ENSP00000302160.3		P62310

Frequencies

GnomAD3 genomes

AF:

0.0223

AC:

3393

AN:

152134

Hom.:

208

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.00450

AC:

149

AN:

33084

American (AMR)

AF:

0.122

AC:

5450

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.00392

AC:

102

AN:

26002

East Asian (EAS)

AF:

0.215

AC:

8511

AN:

39604

South Asian (SAS)

AF:

0.0300

AC:

2573

AN:

85870

European-Finnish (FIN)

AF:

0.0115

AC:

614

AN:

53388

Middle Eastern (MID)

AF:

0.00954

AC:

AN:

5344

European-Non Finnish (NFE)

AF:

0.00404

AC:

4424

AN:

1095336

Other (OTH)

AF:

0.0221

AC:

1321

AN:

59672

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1123

2247

3370

4494

5617

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

368

736

1104

1472

1840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0224

AC:

3406

AN:

152252

Hom.:

209

Cov.:

AF XY:

0.0256

AC XY:

1907

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00602

AC:

250

AN:

41532

American (AMR)

AF:

0.0918

AC:

1405

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3468

East Asian (EAS)

AF:

0.217

AC:

1122

AN:

5170

South Asian (SAS)

AF:

0.0375

AC:

181

AN:

4826

European-Finnish (FIN)

AF:

0.00829

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00443

AC:

301

AN:

68020

Other (OTH)

AF:

0.0208

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

158

316

474

632

790

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0207

Hom.:

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

LINK: link

Submissions by phenotype

not provided

Benign:3

Oct 28, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 09, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 21822670) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.9

(source)

DANN

Benign

0.75

PhyloP100

1.0

PromoterAI

-0.040

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over