chr8-38169822-C-T

Variant names:

• chr8-38169822-C-T
• rs374806513
• NM_014462.3:c.211G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014462.3(LSM1):​c.211G>A​(p.Val71Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LSM1 NM_014462.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.83

Genes affected

LSM1 (HGNC:20472): (LSM1 homolog, mRNA degradation associated) This gene encodes a member of the LSm family of RNA-binding proteins. LSm proteins form stable heteromers that bind specifically to the 3'-terminal oligo(U) tract of U6 snRNA and may play a role in pre-mRNA splicing by mediating U4/U6 snRNP formation. Increased expression of this gene may play a role in cellular transformation and the progression of several malignancies including lung cancer, mesothelioma and breast cancer. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the short arm of chromosome 9. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.906

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSM1	NM_014462.3	c.211G>A	p.Val71Met	missense_variant	Exon 3 of 4	ENST00000311351.9	NP_055277.1
LSM1	NR_045493.1	n.343G>A		non_coding_transcript_exon_variant	Exon 3 of 4
LSM1	NR_045492.2	n.288+2143G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSM1	ENST00000311351.9	c.211G>A	p.Val71Met	missense_variant	Exon 3 of 4	1	NM_014462.3	ENSP00000310596.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 18, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.211G>A (p.V71M) alteration is located in exon 3 (coding exon 3) of the LSM1 gene. This alteration results from a G to A substitution at nucleotide position 211, causing the valine (V) at amino acid position 71 to be replaced by a methionine (M). 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	0.92
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.86	D
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.053	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	0.15	D
MutationAssessor	Pathogenic	3.6	H
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.57
Sift	Benign	0.056	T
Sift4G	Uncertain	0.017	D
Polyphen		0.97	D
Vest4		0.90
MutPred		0.76		Gain of sheet (P = 0.1208);
MVP		0.93
MPC		1.3
ClinPred		0.99	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.83

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: rs374806513; hg19: chr8-38027340;