chr13-32403200-T-C

Variant names:

• chr13-32403200-T-C
• rs770608287
• ENST00000380139.8:c.466A>G

Variant summary

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

The NM_001353628.2(N4BP2L1):​c.742A>G​(p.Lys248Glu) variant causes a missense, splice region 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. 13/19 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. K248Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: N4BP2L1 NM_001353628.2 missense, splice_region
• Scores: Splicing: ADA: 0.002693
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 0 publications found

Genes affected

N4BP2L1 (HGNC:25037): (NEDD4 binding protein 2 like 1)

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=0.08628902).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353628.2. 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
	N4BP2L1	NM_052818.3	MANE Select	c.474A>G	p.Arg158Arg	splice_region synonymous	Exon 5 of 5	NP_438169.2	Q5TBK1-1
	N4BP2L1	NM_001353628.2		c.742A>G	p.Lys248Glu	missense splice_region	Exon 7 of 7	NP_001340557.1
	N4BP2L1	NM_001353630.2		c.572A>G	p.Glu191Gly	missense splice_region	Exon 6 of 6	NP_001340559.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	N4BP2L1	ENST00000380139.8	TSL:1	c.466A>G	p.Lys156Glu	missense splice_region	Exon 5 of 5	ENSP00000369484.3	Q5TBK1-2
	N4BP2L1	ENST00000380130.7	TSL:1 MANE Select	c.474A>G	p.Arg158Arg	splice_region synonymous	Exon 5 of 5	ENSP00000369473.2	Q5TBK1-1
	N4BP2L1	ENST00000380133.6	TSL:1	c.474A>G	p.Arg158Arg	splice_region synonymous	Exon 5 of 6	ENSP00000369476.2	Q5TBK1-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 231662 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	13
DANN	Uncertain	1.0
Eigen	Benign	0.16
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.98	T
PhyloP100		1.0
PROVEAN	Benign	0.67	N
REVEL	Benign	0.012
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.022	D
Polyphen		0.010	B
Vest4		0.32
MutPred		0.42		Gain of catalytic residue at M155 (P = 8e-04)
MVP		0.043
ClinPred		0.15	T
GERP RS		1.9
Mutation Taster		=62/38	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0027
dbscSNV1_RF	Benign	0.12
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: rs770608287; hg19: chr13-32977337;