8-38172008-A-G

Variant names:

• chr8-38172008-A-G
• rs1297220106
• NM_014462.3:c.72T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014462.3(LSM1):​c.72T>C​(p.Asp24Asp) variant causes a synonymous change. The variant allele was found at a frequency of 0.000000685 in 1,459,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LSM1 NM_014462.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSM1	NM_014462.3	c.72T>C	p.Asp24Asp	synonymous_variant	Exon 2 of 4	ENST00000311351.9	NP_055277.1
LSM1	NR_045492.2	n.245T>C		non_coding_transcript_exon_variant	Exon 2 of 3
LSM1	NR_045493.1	n.204T>C		non_coding_transcript_exon_variant	Exon 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSM1	ENST00000311351.9	c.72T>C	p.Asp24Asp	synonymous_variant	Exon 2 of 4	1	NM_014462.3	ENSP00000310596.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459698 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726180

African (AFR) AF: 0.00 AC: 0 AN: 33274

American (AMR) AF: 0.00 AC: 0 AN: 43922

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 85908

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111418

Other (OTH) AF: 0.00 AC: 0 AN: 60320

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1297220106; hg19: chr8-38029526;