16-189998-C-A

Variant names:

• chr16-189998-C-A
• rs146490197
• NM_201412.3:c.944G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_201412.3(LUC7L):​c.944G>T​(p.Arg315Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,438 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. R315Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LUC7L NM_201412.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.98
• Publications: 5 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36394066).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201412.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LUC7L	NM_201412.3	MANE Select	c.944G>T	p.Arg315Leu	missense	Exon 9 of 10	NP_958815.1	Q9NQ29-1
	LUC7L	NM_001320226.2		c.944G>T	p.Arg315Leu	missense	Exon 9 of 10	NP_001307155.1	Q9NQ29-2
	LUC7L	NM_018032.5		c.944G>T	p.Arg315Leu	missense	Exon 9 of 9	NP_060502.1	Q9NQ29-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LUC7L	ENST00000293872.13	TSL:1 MANE Select	c.944G>T	p.Arg315Leu	missense	Exon 9 of 10	ENSP00000293872.8	Q9NQ29-1
	LUC7L	ENST00000337351.8	TSL:1	c.944G>T	p.Arg315Leu	missense	Exon 9 of 9	ENSP00000337507.4	Q9NQ29-2
	LUC7L	ENST00000426094.5	TSL:1	n.*2107G>T		non_coding_transcript_exon	Exon 9 of 10	ENSP00000390953.1	F8WBC1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461438 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726944

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111680

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.0
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.075
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.65	P
Vest4		0.55
MutPred		0.33		Loss of methylation at R315 (P = 0.0348)
MVP		0.74
MPC		0.70
ClinPred		0.81	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.13
Mutation Taster		=46/54	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs146490197; hg19: chr16-239997; COSMIC: COSV53456700; COSMIC: COSV53456700;