7-139422194-T-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016019.5(LUC7L2):c.1033T>A(p.Leu345Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,613,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

LUC7L2
NM_016019.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.12

Publications

0 publications found

Variant links:

Genes affected

LUC7L2 (HGNC:21608): (LUC7 like 2, pre-mRNA splicing factor) This gene encodes a protein that contains a C2H2-type zinc finger, coiled-coil region and arginine, serine-rich (RS) domain. A similar protein in mouse interacts with sodium channel modifier 1, and the encoded protein may be involved in the recognition of non-consensus splice donor sites in association with the U1 snRNP spliceosomal subunit. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

LUC7L2 links:

FMC1-LUC7L2 (HGNC:44671): (FMC1-LUC7L2 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring C7orf55 (chromosome 7 open reading frame 55) and LUC7L2 (LUC7-like 2) genes on chromosome 7. The readthrough transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jul 2012]

FMC1-LUC7L2 links:

ENSG00000310166 (HGNC:):

ENSG00000310166 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05381772).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016019.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LUC7L2	NM_016019.5	MANE Select	c.1033T>A	p.Leu345Ile	missense	Exon 10 of 10	NP_057103.2	Q9Y383-1
FMC1-LUC7L2	NM_001244584.3		c.1231T>A	p.Leu411Ile	missense	Exon 11 of 11	NP_001231513.1
LUC7L2	NM_001270643.2		c.1030T>A	p.Leu344Ile	missense	Exon 11 of 11	NP_001257572.1	Q9Y383-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LUC7L2	ENST00000354926.9	TSL:1 MANE Select	c.1033T>A	p.Leu345Ile	missense	Exon 10 of 10	ENSP00000347005.4	Q9Y383-1
FMC1-LUC7L2	ENST00000541515.3	TSL:2	c.1231T>A	p.Leu411Ile	missense	Exon 11 of 11	ENSP00000440222.1
LUC7L2	ENST00000619796.4	TSL:1	c.1030T>A	p.Leu344Ile	missense	Exon 11 of 11	ENSP00000483438.1	Q9Y383-2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000725

AC:

AN:

248428

AF XY:

0.0000594

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.000159

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000144

AC:

210

AN:

1460894

Hom.:

Cov.:

AF XY:

0.000144

AC XY:

105

AN XY:

726710

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33410

American (AMR)

AF:

0.00

AC:

AN:

44392

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26084

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86034

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.000186

AC:

207

AN:

1111752

Other (OTH)

AF:

0.0000497

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.0000526

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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:

0.000113

Hom.:

Bravo

AF:

0.0000642

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000267

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.0000662

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.013

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.77

M_CAP

Benign

0.0050

MetaRNN

Benign

0.054

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

1.1

PROVEAN

Benign

-0.14

REVEL

Benign

0.049

Sift

Benign

0.11

Sift4G

Benign

0.37

Polyphen

0.033

Vest4

0.23

MVP

0.043

MPC

0.43

ClinPred

0.085

GERP RS

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.039

gMVP

0.059

Mutation Taster

=93/7

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over