NM_052818.3:c.312A>C

Variant names:

• chr13-32407334-T-G
• rs781048243
• NM_052818.3:c.312A>C

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.312A>C​(p.Arg104Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,868 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: N4BP2L1 NM_052818.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.302
• 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=0.19627073).

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.312A>C	p.Arg104Ser	missense	Exon 3 of 5	NP_438169.2	Q5TBK1-1
	N4BP2L1	NM_001353627.2		c.588A>C	p.Arg196Ser	missense	Exon 5 of 7	NP_001340556.1
	N4BP2L1	NM_001353628.2		c.588A>C	p.Arg196Ser	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.312A>C	p.Arg104Ser	missense	Exon 3 of 5	ENSP00000369473.2	Q5TBK1-1
	N4BP2L1	ENST00000380133.6	TSL:1	c.312A>C	p.Arg104Ser	missense	Exon 3 of 6	ENSP00000369476.2	Q5TBK1-1
	N4BP2L1	ENST00000380139.8	TSL:1	c.312A>C	p.Arg104Ser	missense	Exon 3 of 5	ENSP00000369484.3	Q5TBK1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251408 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 0.00000137 AC: 2 AN: 1461868 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.088
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.30
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.26
Sift	Benign	0.070	T
Sift4G	Benign	0.40	T
Polyphen		0.11	B
Vest4		0.56
MutPred		0.53		Loss of MoRF binding (P = 0.0241)
MVP		0.24
MPC		0.64
ClinPred		0.22	T
GERP RS		0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.82
Mutation Taster		=58/42	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs781048243; hg19: chr13-32981471;