4-146189651-A-T

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>T(p.Met80Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000162 in 1,601,388 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. M80V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 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=0.22795987).

BS2

High AC in GnomAdExome4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSM6	NM_007080.3 link	c.238A>T	p.Met80Leu	missense_variant	Exon 4 of 4	ENST00000296581.11	NP_009011.1	P62312
LSM6	XM_017007672.2 link	c.238A>T	p.Met80Leu	missense_variant	Exon 4 of 4		XP_016863161.1	P62312
LSM6	XM_017007673.2 link	c.238A>T	p.Met80Leu	missense_variant	Exon 4 of 4		XP_016863162.1	P62312
LSM6	XR_001741098.2 link	n.342A>T		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>T	p.Met80Leu	missense_variant	Exon 4 of 4	1	NM_007080.3	ENSP00000296581.5		P62312
LSM6	ENST00000649747.1 link	c.238A>T	p.Met80Leu	missense_variant	Exon 4 of 4			ENSP00000497311.1		P62312

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000163

AC:

AN:

244706

AF XY:

0.0000227

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000918

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:

0.000167

GnomAD4 exome

AF:

0.0000166

AC:

AN:

1449244

Hom.:

Cov.:

AF XY:

0.0000208

AC XY:

AN XY:

721058

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32874

American (AMR)

AF:

0.0000699

AC:

AN:

42934

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:

0.000349

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.0000154

AC:

AN:

1105364

Other (OTH)

AF:

0.0000333

AC:

AN:

59984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.429

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:

0.0000131

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 20, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.238A>T (p.M80L) alteration is located in exon 4 (coding exon 3) of the LSM6 gene. This alteration results from a A to T substitution at nucleotide position 238, causing the methionine (M) at amino acid position 80 to be replaced by a leucine (L). 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

0.064

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Benign

-0.11

CADD

Benign

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.015

T;T;T

Eigen

Benign

-0.025

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.0033

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-0.98

PhyloP100

7.0

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.060

N;.;N

REVEL

Benign

0.17

Sift

Benign

1.0

T;.;T

Sift4G

Benign

0.77

T;.;T

Polyphen

0.0

B;B;B

Vest4

0.54

MutPred

0.35

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);

MVP

0.40

MPC

1.1

ClinPred

0.62

GERP RS

6.0

Varity_R

0.23

gMVP

0.44

Mutation Taster

=85/15

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over