7-139422321-G-A

Position:

chr7-139422321-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016019.5(LUC7L2):c.1160G>A(p.Arg387His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000862 in 1,612,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000083 ( 0 hom. )

Consequence

LUC7L2
NM_016019.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.92

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:

LUC7L2 (HGNC:):

LUC7L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.077911615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LUC7L2	NM_016019.5 linkuse as main transcript	c.1160G>A	p.Arg387His	missense_variant	10/10	ENST00000354926.9	NP_057103.2	Q9Y383-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LUC7L2	ENST00000354926.9 linkuse as main transcript	c.1160G>A	p.Arg387His	missense_variant	10/10	1	NM_016019.5	ENSP00000347005.4		Q9Y383-1
FMC1-LUC7L2	ENST00000541515.3 linkuse as main transcript	c.1358G>A	p.Arg453His	missense_variant	11/11	2		ENSP00000440222.1		A0A0A6YYJ8

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000971

AC:

AN:

247120

Hom.:

AF XY:

0.0000671

AC XY:

AN XY:

134148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000414

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000623

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000829

AC:

121

AN:

1460112

Hom.:

Cov.:

AF XY:

0.0000592

AC XY:

AN XY:

726388

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000385

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000720

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000118

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000155

Hom.:

Bravo

AF:

0.000155

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000241

AC:

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2021

The c.1160G>A (p.R387H) alteration is located in exon 10 (coding exon 10) of the LUC7L2 gene. This alteration results from a G to A substitution at nucleotide position 1160, causing the arginine (R) at amino acid position 387 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

.;.;T;.;.

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.85

.;D;D;D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.078

T;T;T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.2

.;.;M;.;.

PROVEAN

Benign

-0.66

N;.;N;.;N

REVEL

Benign

0.13

Sift

Uncertain

0.026

D;.;D;.;D

Sift4G

Benign

0.082

T;T;T;T;T

Polyphen

0.95, 0.92

.;P;P;.;.

Vest4

0.23

MVP

0.28

MPC

0.49, 0.47

ClinPred

0.066

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.068

gMVP

0.16

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