chr16-189317-T-C

Position:

• chr16-189317-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_201412.3(LUC7L):​c.997A>G​(p.Arg333Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LUC7L NM_201412.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.79

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 (HGNC:):

ACMG classification

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=0.1993384).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LUC7L	NM_201412.3	c.997A>G	p.Arg333Gly	missense_variant	10/10	ENST00000293872.13	NP_958815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LUC7L	ENST00000293872.13	c.997A>G	p.Arg333Gly	missense_variant	10/10	1	NM_201412.3	ENSP00000293872.8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459976 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726170

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: 9.00e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 11, 2024

The c.997A>G (p.R333G) alteration is located in exon 10 (coding exon 10) of the LUC7L gene. This alteration results from a A to G substitution at nucleotide position 997, causing the arginine (R) at amino acid position 333 to be replaced by a glycine (G). 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	0.092
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.25	T;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.049
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.16
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.049	D;D
Polyphen		0.18	B;.
Vest4		0.53
MutPred		0.24		Gain of relative solvent accessibility (P = 0.0166);.;
MVP		0.69
MPC		0.73
ClinPred		0.68	D
GERP RS		4.0
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1
Varity_R		0.33
gMVP		0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-239316; COSMIC: COSV53459564; COSMIC: COSV53459564;