rs775533753

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr13-32427991-C-A
• chr13-32427991-C-G
• chr13-32427991-C-T

Variant summary

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

The NM_001353629.2(N4BP2L1):​c.-349G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,404,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: N4BP2L1 NM_001353629.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.274645).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353629.2. 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.92G>T	p.Arg31Leu	missense	Exon 1 of 5	NP_438169.2	Q5TBK1-1
	N4BP2L1	NM_001353629.2		c.-349G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_001340558.1
	N4BP2L1	NM_001353631.2		c.-349G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_001340560.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	N4BP2L1	ENST00000380130.7	TSL:1 MANE Select	c.92G>T	p.Arg31Leu	missense	Exon 1 of 5	ENSP00000369473.2	Q5TBK1-1
	N4BP2L1	ENST00000380133.6	TSL:1	c.92G>T	p.Arg31Leu	missense	Exon 1 of 6	ENSP00000369476.2	Q5TBK1-1
	N4BP2L1	ENST00000380139.8	TSL:1	c.92G>T	p.Arg31Leu	missense	Exon 1 of 5	ENSP00000369484.3	Q5TBK1-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000118 AC: 2 AN: 168922 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000433

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 AF: 0.00000214 AC: 3 AN: 1404366 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 697506

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

American (AMR) AF: 0.0000287 AC: 1 AN: 34838

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 34044

South Asian (SAS) AF: 0.0000123 AC: 1 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: 0.0000173 AC: 1 AN: 57766

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000776 Hom.: 0

Bravo AF: 0.00000756

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	0.22
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.55	T
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.46	N
PhyloP100		1.4
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.089
Sift	Benign	0.035	D
Sift4G	Benign	0.10	T
Polyphen		0.99	D
Vest4		0.48
MutPred		0.33		Gain of catalytic residue at P28 (P = 0)
MVP		0.043
MPC		1.1
ClinPred		0.65	D
GERP RS		3.7
PromoterAI		-0.029	Neutral
Varity_R		0.083
gMVP		0.43
Mutation Taster		=87/13	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;