NM_201412.3:c.965C>T

Variant names:

• chr16-189977-G-A
• rs770266344
• NM_201412.3:c.965C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_201412.3(LUC7L):​c.965C>T​(p.Ala322Val) variant causes a missense change. The variant allele was found at a frequency of 0.000102 in 1,611,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: LUC7L NM_201412.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.78
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1519194).

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.965C>T	p.Ala322Val	missense	Exon 9 of 10	NP_958815.1	Q9NQ29-1
	LUC7L	NM_001320226.2		c.965C>T	p.Ala322Val	missense	Exon 9 of 10	NP_001307155.1	Q9NQ29-2
	LUC7L	NM_018032.5		c.965C>T	p.Ala322Val	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.965C>T	p.Ala322Val	missense	Exon 9 of 10	ENSP00000293872.8	Q9NQ29-1
	LUC7L	ENST00000337351.8	TSL:1	c.965C>T	p.Ala322Val	missense	Exon 9 of 9	ENSP00000337507.4	Q9NQ29-2
	LUC7L	ENST00000426094.5	TSL:1	n.*2128C>T		non_coding_transcript_exon	Exon 9 of 10	ENSP00000390953.1	F8WBC1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152114 Hom.: 0 Cov.: 31

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: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000519 AC: 13 AN: 250578 AF XY: 0.0000443

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000106 AC: 154 AN: 1459498 Hom.: 0 Cov.: 31 AF XY: 0.000105 AC XY: 76 AN XY: 725614

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39642

South Asian (SAS) AF: 0.0000581 AC: 5 AN: 86114

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53318

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5750

European-Non Finnish (NFE) AF: 0.000129 AC: 143 AN: 1110232

Other (OTH) AF: 0.0000498 AC: 3 AN: 60276

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152114 Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4 AN XY: 74298

African (AFR) AF: 0.00 AC: 0 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000169 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.037
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		6.8
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.045
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.16	T
Polyphen		0.33	B
Vest4		0.19
MVP		0.67
MPC		0.56
ClinPred		0.26	T
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.16
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs770266344; hg19: chr16-239976; COSMIC: COSV53458474; COSMIC: COSV53458474;