NM_014462.3:c.43_45delGACinsAAT

Variant names:

• chr8-38176276-GTC-ATT
• NM_014462.3:c.43_45delGACinsAAT
• LSM1 p.Asp15Asn

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP2

The NM_014462.3(LSM1):​c.43_45delGACinsAAT​(p.Asp15Asn) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LSM1 NM_014462.3 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.67
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 1.0017 (below the threshold of 3.09). Trascript score misZ: 0.15829 (below the threshold of 3.09).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014462.3. 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
	LSM1	NM_014462.3	MANE Select	c.43_45delGACinsAAT	p.Asp15Asn	missense splice_region	N/A	NP_055277.1	A0A0S2Z590
	LSM1	NR_045492.2		n.216_218delGACinsAAT		splice_region non_coding_transcript_exon	Exon 1 of 3
	LSM1	NR_045493.1		n.178+275_178+277delGACinsAAT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSM1	ENST00000311351.9	TSL:1 MANE Select	c.43_45delGACinsAAT	p.Asp15Asn	missense splice_region	N/A	ENSP00000310596.4	O15116
	LSM1	ENST00000520755.5	TSL:1	c.43_45delGACinsAAT	p.Asp15Asn	missense splice_region	N/A	ENSP00000430021.1	E5RH18
	LSM1	ENST00000520286.5	TSL:1	n.178+275_178+277delGACinsAAT		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-38033794;