NM_007080.3:c.238A>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_007080.3(LSM6):c.238A>G(p.Met80Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000237 in 1,601,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M80L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

LSM6
NM_007080.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.00

Publications

0 publications found

Variant links:

Genes affected

LSM6 (HGNC:17017): (LSM6 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]

LSM6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.081389755).

BS2

High AC in GnomAd4 at 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSM6	NM_007080.3 link	c.238A>G	p.Met80Val	missense_variant	Exon 4 of 4	ENST00000296581.11	NP_009011.1	P62312
LSM6	XM_017007672.2 link	c.238A>G	p.Met80Val	missense_variant	Exon 4 of 4		XP_016863161.1	P62312
LSM6	XM_017007673.2 link	c.238A>G	p.Met80Val	missense_variant	Exon 4 of 4		XP_016863162.1	P62312
LSM6	XR_001741098.2 link	n.342A>G		non_coding_transcript_exon_variant	Exon 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSM6	ENST00000296581.11 link	c.238A>G	p.Met80Val	missense_variant	Exon 4 of 4	1	NM_007080.3	ENSP00000296581.5		P62312
LSM6	ENST00000649747.1 link	c.238A>G	p.Met80Val	missense_variant	Exon 4 of 4			ENSP00000497311.1		P62312

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000368

AC:

AN:

244706

AF XY:

0.0000378

show subpopulations

Gnomad AFR exome

AF:

0.000560

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000690

AC:

AN:

1449246

Hom.:

Cov.:

AF XY:

0.00000555

AC XY:

AN XY:

721058

show subpopulations

African (AFR)

AF:

0.000213

AC:

AN:

32874

American (AMR)

AF:

0.00

AC:

AN:

42936

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25980

East Asian (EAS)

AF:

0.00

AC:

AN:

39476

South Asian (SAS)

AF:

0.00

AC:

AN:

83594

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105364

Other (OTH)

AF:

0.0000500

AC:

AN:

59984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.420

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:

0.000184

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.000674

AC:

AN:

41558

American (AMR)

AF:

0.00

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

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:

0.000293

Hom.:

Bravo

AF:

0.000170

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 25, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.238A>G (p.M80V) alteration is located in exon 4 (coding exon 3) of the LSM6 gene. This alteration results from a A to G substitution at nucleotide position 238, causing the methionine (M) at amino acid position 80 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.023

T;T;T

Eigen

Benign

0.074

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.0026

MetaRNN

Benign

0.081

T;T;T

MetaSVM

Benign

-0.94

PhyloP100

7.0

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.16

N;.;N

REVEL

Benign

0.17

Sift

Benign

0.41

T;.;T

Sift4G

Benign

0.49

T;.;T

Polyphen

0.0

B;B;B

Vest4

0.35

MVP

0.33

MPC

1.2

ClinPred

0.18

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.24

gMVP

0.60

Mutation Taster

=82/18

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over