19-2321785-CC-TA

Variant names:

• chr19-2321785-CC-TA
• NM_016199.3:c.206_207delGGinsTA
• LSM7 p.Arg69Leu

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM5 PP2

The NM_016199.3(LSM7):​c.206_207delGGinsTA​(p.Arg69Leu) variant causes a missense 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R69Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LSM7 NM_016199.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.51
• Publications: 0 publications found

Genes affected

LSM7 (HGNC:20470): (LSM7 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]

ENSG00000273734 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM5: Other missense variant is known to change same aminoacid residue: Variant chr19-2321786-C-G is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 996338.Status of the report is criteria_provided_single_submitter, 1 stars.
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 2 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 1.4328 (below the threshold of 3.09). Trascript score misZ: -0.025562 (below the threshold of 3.09).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016199.3. 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
	LSM7	NM_016199.3	MANE Select	c.206_207delGGinsTA	p.Arg69Leu	missense	N/A	NP_057283.1	Q9UK45

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSM7	ENST00000252622.15	TSL:1 MANE Select	c.206_207delGGinsTA	p.Arg69Leu	missense	N/A	ENSP00000252622.8	Q9UK45
	LSM7	ENST00000587502.2	TSL:1	c.44_45delGGinsTA	p.Arg15Leu	missense	N/A	ENSP00000485007.1	A0A087X2I5
	ENSG00000273734	ENST00000621615.1	TSL:2	n.147-12817_147-12816delCCinsTA		intron	N/A	ENSP00000481965.1	A0A087WYN8

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		5.5

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: chr19-2321784;