13-32427991-C-G

Variant names:

• chr13-32427991-C-G
• rs775533753
• NM_052818.3:c.92G>C

Variant summary

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

The NM_052818.3(N4BP2L1):​c.92G>C​(p.Arg31Pro) 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. 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. R31L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: N4BP2L1 NM_052818.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 1 publications found

Genes affected

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

ENSG00000270008 (HGNC:):

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=0.3090446).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052818.3. 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
	N4BP2L1	NM_052818.3	MANE Select	c.92G>C	p.Arg31Pro	missense	Exon 1 of 5	NP_438169.2	Q5TBK1-1
	N4BP2L1	NM_001353627.2		c.92G>C	p.Arg31Pro	missense	Exon 1 of 7	NP_001340556.1
	N4BP2L1	NM_001353628.2		c.92G>C	p.Arg31Pro	missense	Exon 1 of 7	NP_001340557.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	N4BP2L1	ENST00000380130.7	TSL:1 MANE Select	c.92G>C	p.Arg31Pro	missense	Exon 1 of 5	ENSP00000369473.2	Q5TBK1-1
	N4BP2L1	ENST00000380133.6	TSL:1	c.92G>C	p.Arg31Pro	missense	Exon 1 of 6	ENSP00000369476.2	Q5TBK1-1
	N4BP2L1	ENST00000380139.8	TSL:1	c.92G>C	p.Arg31Pro	missense	Exon 1 of 5	ENSP00000369484.3	Q5TBK1-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 168922 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1404368 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 697506

African (AFR) AF: 0.00 AC: 0 AN: 29708

American (AMR) AF: 0.00 AC: 0 AN: 34838

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24196

East Asian (EAS) AF: 0.00 AC: 0 AN: 34046

South Asian (SAS) AF: 0.00 AC: 0 AN: 81550

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5506

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1085798

Other (OTH) AF: 0.00 AC: 0 AN: 57766

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000847 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.45	T
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.4
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.95	N
REVEL	Uncertain	0.33
Sift	Benign	0.21	T
Sift4G	Benign	0.28	T
Polyphen		1.0	D
Vest4		0.42
MutPred		0.32		Gain of catalytic residue at P28 (P = 0)
MVP		0.043
MPC		1.6
ClinPred		0.76	D
GERP RS		3.7
PromoterAI		0.044	Neutral
Varity_R		0.22
gMVP		0.40
Mutation Taster		=73/27	polymorphism

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: rs775533753; hg19: chr13-33002128;