13-32407279-C-A

Variant names:

• chr13-32407279-C-A
• rs752396467
• NM_052818.3:c.367G>T

Variant summary

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

The NM_052818.3(N4BP2L1):​c.367G>T​(p.Ala123Ser) 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. A123T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: N4BP2L1 NM_052818.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.00
• Publications: 1 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=0.2516731).

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.367G>T	p.Ala123Ser	missense	Exon 3 of 5	NP_438169.2	Q5TBK1-1
	N4BP2L1	NM_001353627.2		c.643G>T	p.Ala215Ser	missense	Exon 5 of 7	NP_001340556.1
	N4BP2L1	NM_001353628.2		c.643G>T	p.Ala215Ser	missense	Exon 5 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.367G>T	p.Ala123Ser	missense	Exon 3 of 5	ENSP00000369473.2	Q5TBK1-1
	N4BP2L1	ENST00000380133.6	TSL:1	c.367G>T	p.Ala123Ser	missense	Exon 3 of 6	ENSP00000369476.2	Q5TBK1-1
	N4BP2L1	ENST00000380139.8	TSL:1	c.367G>T	p.Ala123Ser	missense	Exon 3 of 5	ENSP00000369484.3	Q5TBK1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.0
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.21
Sift	Benign	0.21	T
Sift4G	Benign	0.24	T
Polyphen		0.75	P
Vest4		0.46
MutPred		0.35		Gain of catalytic residue at N120 (P = 0)
MVP		0.20
MPC		0.92
ClinPred		0.92	D
GERP RS		4.5
Varity_R		0.41
gMVP		0.76
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs752396467; hg19: chr13-32981416;