rs750219615

Variant names:

• chr19-2324173-C-A
• NM_016199.3:c.121G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-2324173-C-A
• chr19-2324173-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_016199.3(LSM7):​c.121G>T​(p.Asp41Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000028 in 1,430,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: LSM7 NM_016199.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.61

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

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.993

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSM7	NM_016199.3	c.121G>T	p.Asp41Tyr	missense_variant	Exon 3 of 4	ENST00000252622.15	NP_057283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSM7	ENST00000252622.15	c.121G>T	p.Asp41Tyr	missense_variant	Exon 3 of 4	1	NM_016199.3	ENSP00000252622.8
ENSG00000273734	ENST00000621615.1	n.147-10429C>A		intron_variant	Intron 1 of 7	2		ENSP00000481965.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000280 AC: 4 AN: 1430040 Hom.: 0 Cov.: 33 AF XY: 0.00000282 AC XY: 2 AN XY: 708366

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000365

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.82	D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Pathogenic	0.49	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Pathogenic	0.95	D
MutationAssessor	Pathogenic	5.2	H
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-8.3	D
REVEL	Pathogenic	0.89
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.94		Loss of ubiquitination at K38 (P = 0.1264);
MVP		0.96
MPC		2.2
ClinPred		1.0	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.97
gMVP		0.96

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-2324172;