Genetic Variant NM_016199.3:c.121G>A (chr19-2324173-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PP3_StrongPP5BS2_Supporting

The NM_016199.3(LSM7):c.121G>A(p.Asp41Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000259 in 1,582,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

LSM7
NM_016199.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.61

Variant links:

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]

LSM7 links:

ENSG00000273734 (HGNC:):

ENSG00000273734 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.992

PP5

Variant 19-2324173-C-T is Pathogenic according to our data. Variant chr19-2324173-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 996070.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 6 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSM7	NM_016199.3 link	c.121G>A	p.Asp41Asn	missense_variant	Exon 3 of 4	ENST00000252622.15	NP_057283.1	Q9UK45

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSM7	ENST00000252622.15 link	c.121G>A	p.Asp41Asn	missense_variant	Exon 3 of 4	1	NM_016199.3	ENSP00000252622.8		Q9UK45
ENSG00000273734	ENST00000621615.1 link	n.147-10429C>T		intron_variant	Intron 1 of 7	2		ENSP00000481965.1		A0A087WYN8

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000397

AC:

AN:

201434

Hom.:

AF XY:

0.0000461

AC XY:

AN XY:

108368

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000171

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000688

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000227

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000245

AC:

AN:

1430038

Hom.:

Cov.:

AF XY:

0.0000212

AC XY:

AN XY:

708366

show subpopulations

Gnomad4 AFR exome

AF:

0.0000306

Gnomad4 AMR exome

AF:

0.000125

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000263

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000237

Gnomad4 OTH exome

AF:

0.0000338

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151980

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000167

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Leukodystrophy

Pathogenic:1

MyeliNeuroGene Lab, McGill University Health Center Research Institute

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.82

Eigen

Pathogenic

0.93

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

M_CAP

Pathogenic

0.49

MetaRNN

Pathogenic

0.99

MetaSVM

Pathogenic

0.87

MutationAssessor

Pathogenic

4.7

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-4.6

REVEL

Pathogenic

0.79

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.92

MutPred

0.96

Gain of sheet (P = 0.0827);

MVP

0.92

MPC

1.1

ClinPred

0.99

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.79

gMVP

0.91

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over