3-100451848-G-C

Position:

• chr3-100451848-G-C

Variant summary

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

The NM_001085451.2(LNP1):​c.286G>C​(p.Glu96Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: LNP1 NM_001085451.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.32

Genes affected

LNP1 (HGNC:28014): (leukemia NUP98 fusion partner 1)

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=0.16066492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LNP1	NM_001085451.2	c.286G>C	p.Glu96Gln	missense_variant	3/4	ENST00000383693.8	NP_001078920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LNP1	ENST00000383693.8	c.286G>C	p.Glu96Gln	missense_variant	3/4	1	NM_001085451.2	ENSP00000373191.3
LNP1	ENST00000489752.1	c.325G>C	p.Glu109Gln	missense_variant	3/4	5		ENSP00000417985.1
LNP1	ENST00000466996.5	n.*98G>C		non_coding_transcript_exon_variant	3/4	5		ENSP00000419213.1
LNP1	ENST00000466996.5	n.*98G>C		3_prime_UTR_variant	3/4	5		ENSP00000419213.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 0

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

Dec 07, 2021

The c.286G>C (p.E96Q) alteration is located in exon 3 (coding exon 2) of the LNP1 gene. This alteration results from a G to C substitution at nucleotide position 286, causing the glutamic acid (E) at amino acid position 96 to be replaced by a glutamine (Q). 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	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.071
Sift	Benign	0.058	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.99	D;.
Vest4		0.17
MutPred		0.080		Gain of glycosylation at S93 (P = 0.0018);.;
MVP		0.085
MPC		0.62
ClinPred		0.83	D
GERP RS		4.4
Varity_R		0.12
gMVP		0.040

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: chr3-100170692;