Genetic Variant LUC7L:p.Arg267Cys (chr16-190548-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_201412.3(LUC7L):c.799C>T(p.Arg267Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,461,432 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 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LUC7L
NM_201412.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.56

Variant links:

Genes affected

LUC7L (HGNC:6723): (LUC7 like) The LUC7L gene may represent a mammalian heterochromatic gene, encoding a putative RNA-binding protein similar to the yeast Luc7p subunit of the U1 snRNP splicing complex that is normally required for 5-prime splice site selection (Tufarelli et al., 2001 [PubMed 11170747]).[supplied by OMIM, Mar 2008]

LUC7L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38017944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LUC7L	NM_201412.3 link	c.799C>T	p.Arg267Cys	missense_variant	Exon 8 of 10	ENST00000293872.13	NP_958815.1	Q9NQ29-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LUC7L	ENST00000293872.13 link	c.799C>T	p.Arg267Cys	missense_variant	Exon 8 of 10	1	NM_201412.3	ENSP00000293872.8		Q9NQ29-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152114

Hom.:

Cov.:

FAILED QC

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251390

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135896

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461432

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727042

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74306

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.799C>T (p.R267C) alteration is located in exon 8 (coding exon 8) of the LUC7L gene. This alteration results from a C to T substitution at nucleotide position 799, causing the arginine (R) at amino acid position 267 to be replaced by a cysteine (C). 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

0.32

BayesDel_addAF

Uncertain

0.059

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

D;.;.;T;.;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

D;.;D;D;D;D

M_CAP

Benign

0.050

MetaRNN

Benign

0.38

T;T;T;T;T;T

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.8

L;L;L;.;.;.

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-2.8

D;D;D;D;D;D

REVEL

Benign

0.25

Sift

Benign

0.19

T;T;T;D;T;D

Sift4G

Uncertain

0.024

D;D;D;T;D;.

Polyphen

1.0

D;.;.;.;.;.

Vest4

0.36

MutPred

0.50

Gain of catalytic residue at R267 (P = 0.0475);Gain of catalytic residue at R267 (P = 0.0475);Gain of catalytic residue at R267 (P = 0.0475);.;.;.;

MVP

0.71

MPC

0.77

ClinPred

0.91

GERP RS

4.8

Varity_R

0.23

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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