rs753016350

Variant names:

• chr7-139417656-C-A
• rs753016350
• NM_016019.5:c.928C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-139417656-C-A
• chr7-139417656-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016019.5(LUC7L2):​c.928C>A​(p.Arg310Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,774 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict 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. R310C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (1 hom.)
• Consequence: LUC7L2 NM_016019.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44
• Publications: 0 publications found

Genes affected

LUC7L2 (HGNC:21608): (LUC7 like 2, pre-mRNA splicing factor) This gene encodes a protein that contains a C2H2-type zinc finger, coiled-coil region and arginine, serine-rich (RS) domain. A similar protein in mouse interacts with sodium channel modifier 1, and the encoded protein may be involved in the recognition of non-consensus splice donor sites in association with the U1 snRNP spliceosomal subunit. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

FMC1-LUC7L2 (HGNC:44671): (FMC1-LUC7L2 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring C7orf55 (chromosome 7 open reading frame 55) and LUC7L2 (LUC7-like 2) genes on chromosome 7. The readthrough transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jul 2012]

ENSG00000310166 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23143286).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016019.5. 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
	LUC7L2	NM_016019.5	MANE Select	c.928C>A	p.Arg310Ser	missense	Exon 9 of 10	NP_057103.2	Q9Y383-1
	FMC1-LUC7L2	NM_001244584.3		c.1126C>A	p.Arg376Ser	missense	Exon 10 of 11	NP_001231513.1
	LUC7L2	NM_001270643.2		c.925C>A	p.Arg309Ser	missense	Exon 10 of 11	NP_001257572.1	Q9Y383-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LUC7L2	ENST00000354926.9	TSL:1 MANE Select	c.928C>A	p.Arg310Ser	missense	Exon 9 of 10	ENSP00000347005.4	Q9Y383-1
	FMC1-LUC7L2	ENST00000541515.3	TSL:2	c.1126C>A	p.Arg376Ser	missense	Exon 10 of 11	ENSP00000440222.1
	LUC7L2	ENST00000619796.4	TSL:1	c.925C>A	p.Arg309Ser	missense	Exon 10 of 11	ENSP00000483438.1	Q9Y383-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461774 Hom.: 1 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727190

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111920

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Benign	0.80
DEOGEN2	Benign	0.038	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.4
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.093
Sift	Benign	0.66	T
Sift4G	Uncertain	0.050	T
Polyphen		0.99	D
Vest4		0.49
MutPred		0.34		Gain of phosphorylation at R310 (P = 1e-04)
MVP		0.11
MPC		0.44
ClinPred		0.79	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.30
Mutation Taster		=49/51	disease causing

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

Other links and lift over

dbSNP: rs753016350; hg19: chr7-139102402;