rs750219615

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 6P and 1B. PP2PP3_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:2

Conservation

PhyloP100: 6.61

Publications

3 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

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).

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 VariationId 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.

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.121G>A	p.Asp41Asn	missense	Exon 3 of 4	NP_057283.1	Q9UK45

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LSM7	ENST00000252622.15	TSL:1 MANE Select	c.121G>A	p.Asp41Asn	missense	Exon 3 of 4	ENSP00000252622.8	Q9UK45
LSM7	ENST00000587502.2	TSL:1	c.-42G>A		5_prime_UTR	Exon 2 of 3	ENSP00000485007.1	A0A087X2I5
ENSG00000273734	ENST00000621615.1	TSL:2	n.147-10429C>T		intron	N/A	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

GnomAD2 exomes

AF:

0.0000397

AC:

AN:

201434

AF XY:

0.0000461

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 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

African (AFR)

AF:

0.0000306

AC:

AN:

32684

American (AMR)

AF:

0.000125

AC:

AN:

40058

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25622

East Asian (EAS)

AF:

0.0000263

AC:

AN:

37988

South Asian (SAS)

AF:

0.00

AC:

AN:

81386

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50960

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.0000237

AC:

AN:

1096376

Other (OTH)

AF:

0.0000338

AC:

AN:

59230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151980

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41370

American (AMR)

AF:

0.000262

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000167

AC:

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Leukodystrophy (1)

LSM7-related leukodystrophy and cerebellar atrophy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

(source)

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

PhyloP100

6.6

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

Mutation Taster

=31/69

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over