19-34221682-CGC-TCG

Variant names:

• chr19-34221682-CGC-TCG
• NM_015578.4:c.1312_1314delCGCinsTCG
• LSM14A p.Arg438Ser

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_015578.4(LSM14A):​c.1312_1314delCGCinsTCG​(p.Arg438Ser) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 32)
• Consequence: LSM14A NM_015578.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.16
• Publications: 0 publications found

Genes affected

LSM14A (HGNC:24489): (LSM14A mRNA processing body assembly factor) Sm-like proteins were identified in a variety of organisms based on sequence homology with the Sm protein family (see SNRPD2; 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, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015578.4. 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
	LSM14A	NM_015578.4	MANE Select	c.1312_1314delCGCinsTCG	p.Arg438Ser	missense	N/A	NP_056393.2	Q8ND56-2
	LSM14A	NM_001384420.1		c.1312_1314delCGCinsTCG	p.Arg438Ser	missense	N/A	NP_001371349.1
	LSM14A	NM_001114093.3		c.1312_1314delCGCinsTCG	p.Arg438Ser	missense	N/A	NP_001107565.1	Q8ND56-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSM14A	ENST00000544216.8	TSL:1 MANE Select	c.1312_1314delCGCinsTCG	p.Arg438Ser	missense	N/A	ENSP00000446271.2	Q8ND56-2
	LSM14A	ENST00000433627.9	TSL:1	c.1312_1314delCGCinsTCG	p.Arg438Ser	missense	N/A	ENSP00000413964.3	Q8ND56-1
	LSM14A	ENST00000906057.1		c.1309_1311delCGCinsTCG	p.Arg437Ser	missense	N/A	ENSP00000576116.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.2

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: chr19-34712587;