chr3-14181574-C-T

Variant names:

• chr3-14181574-C-T
• rs34724908
• NM_014463.3:c.36C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_014463.3(LSM3):​c.36C>T​(p.Asn12Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00363 in 1,611,216 control chromosomes in the GnomAD database, including 201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (100 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (101 hom.)
• Consequence: LSM3 NM_014463.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.90
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 3-14181574-C-T is Benign according to our data. Variant chr3-14181574-C-T is described in ClinVar as Benign. ClinVar VariationId is 775193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.9 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0663 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014463.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSM3	NM_014463.3	MANE Select	c.36C>T	p.Asn12Asn	synonymous	Exon 2 of 4	NP_055278.1	P62310

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSM3	ENST00000306024.4	TSL:1 MANE Select	c.36C>T	p.Asn12Asn	synonymous	Exon 2 of 4	ENSP00000302160.3	P62310
	LSM3	ENST00000907171.1		c.36C>T	p.Asn12Asn	synonymous	Exon 2 of 3	ENSP00000577230.1
	LSM3	ENST00000907170.1		c.22-2363C>T		intron	N/A	ENSP00000577229.1

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2993 AN: 152176 Hom.: 101 Cov.: 32

Gnomad AFR AF: 0.0681

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00844

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.00524 AC: 1315 AN: 251064 AF XY: 0.00391

Gnomad AFR exome AF: 0.0717

Gnomad AMR exome AF: 0.00318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00194 AC: 2837 AN: 1458922 Hom.: 101 Cov.: 29 AF XY: 0.00173 AC XY: 1253 AN XY: 725996

African (AFR) AF: 0.0689 AC: 2295 AN: 33324

American (AMR) AF: 0.00374 AC: 167 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00382 AC: 22 AN: 5758

European-Non Finnish (NFE) AF: 0.0000622 AC: 69 AN: 1109528

Other (OTH) AF: 0.00450 AC: 271 AN: 60256

GnomAD4 genome AF: 0.0198 AC: 3014 AN: 152294 Hom.: 100 Cov.: 32 AF XY: 0.0189 AC XY: 1411 AN XY: 74470

African (AFR) AF: 0.0684 AC: 2840 AN: 41546

American (AMR) AF: 0.00843 AC: 129 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68024

Other (OTH) AF: 0.0151 AC: 32 AN: 2114

Alfa AF: 0.0112 Hom.: 34

Bravo AF: 0.0225

Asia WGS AF: 0.00693 AC: 25 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	8.1
DANN	Benign	0.84
PhyloP100		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34724908; hg19: chr3-14223074;