13-32442975-T-G

Variant names:

• chr13-32442975-T-G
• rs201002215
• ENST00000380121.7:n.1533A>C

Variant summary

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

The NM_001320836.3(N4BP2L2):​c.2849A>C​(p.Asn950Thr) 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. 14/18 in silico tools predict 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. N950I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: N4BP2L2 NM_001320836.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• Publications: 1 publications found

Genes affected

N4BP2L2 (HGNC:26916): (NEDD4 binding protein 2 like 2) Enables enzyme binding activity. Involved in negative regulation of hematopoietic stem cell differentiation and positive regulation of hematopoietic stem cell proliferation. Located in nucleus. Part of transcription repressor complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.06913602).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320836.3. 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
	N4BP2L2	NM_001320836.3		c.2849A>C	p.Asn950Thr	missense	Exon 7 of 10	NP_001307765.1
	N4BP2L2	NM_001387001.1		c.2849A>C	p.Asn950Thr	missense	Exon 7 of 10	NP_001373930.1
	N4BP2L2	NM_001387002.1		c.2849A>C	p.Asn950Thr	missense	Exon 7 of 10	NP_001373931.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	N4BP2L2	ENST00000380121.7	TSL:1	n.1533A>C		non_coding_transcript_exon	Exon 5 of 8
	N4BP2L2	ENST00000399396.7	TSL:5	c.1562A>C	p.Asn521Thr	missense	Exon 7 of 10	ENSP00000382328.3	Q92802-3
	N4BP2L2	ENST00000357505.10	TSL:2	c.1517A>C	p.Asn506Thr	missense	Exon 7 of 10	ENSP00000350104.6	B4DPY1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248856 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: 0.00000887

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.6
DANN	Benign	0.82
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.041
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.045
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.040	D
Polyphen		0.16	B
Vest4		0.19
MutPred		0.20		Gain of catalytic residue at L509 (P = 0)
MVP		0.15
MPC		0.038
ClinPred		0.047	T
GERP RS		-1.5
gMVP		0.027
Mutation Taster		=99/1	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs201002215; hg19: chr13-33017112;