16-190067-C-G

Variant names:

• chr16-190067-C-G
• NM_201412.3:c.875G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_201412.3(LUC7L):​c.875G>C​(p.Arg292Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R292Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LUC7L NM_201412.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.41

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]

ACMG classification

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=0.27437645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LUC7L	NM_201412.3	c.875G>C	p.Arg292Pro	missense_variant	Exon 9 of 10	ENST00000293872.13	NP_958815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LUC7L	ENST00000293872.13	c.875G>C	p.Arg292Pro	missense_variant	Exon 9 of 10	1	NM_201412.3	ENSP00000293872.8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461422 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727034

Gnomad4 AFR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.17	T;.;.;T;.
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.76	T;.;T;T;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.27	T;T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.3	M;M;M;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.6	N;D;D;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.0050	D;T;T;T;T
Sift4G	Uncertain	0.028	D;D;D;T;D
Polyphen		0.0020	B;.;.;.;.
Vest4		0.47
MutPred		0.21		Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);.;.;
MVP		0.78
MPC		0.82
ClinPred		0.84	D
GERP RS		5.2
Varity_R		0.56
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-240066;