Genetic Variant NABP2:p.Leu155Met (chr12-56229040-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024068.4(NABP2):c.463C>A(p.Leu155Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

NABP2
NM_024068.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.66

Variant links:

Genes affected

NABP2 (HGNC:28412): (nucleic acid binding protein 2) Single-stranded DNA (ssDNA)-binding proteins, such as OBFC2B, are ubiquitous and essential for a variety of DNA metabolic processes, including replication, recombination, and detection and repair of damage (Richard et al., 2008 [PubMed 18449195]).[supplied by OMIM, Jun 2008]

NABP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21767259).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NABP2	NM_024068.4 link	c.463C>A	p.Leu155Met	missense_variant	Exon 7 of 7	ENST00000267023.9	NP_076973.1	Q9BQ15-1A0A024RB89

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NABP2	ENST00000267023.9 link	c.463C>A	p.Leu155Met	missense_variant	Exon 7 of 7	1	NM_024068.4	ENSP00000267023.4	Q9BQ15-1
NABP2	ENST00000380198.6 link	c.463C>A	p.Leu155Met	missense_variant	Exon 6 of 6	1		ENSP00000369545.2	Q9BQ15-1
NABP2	ENST00000341463.5 link	c.463C>A	p.Leu155Met	missense_variant	Exon 7 of 7	3		ENSP00000368862.3	Q9BQ15-1
NABP2	ENST00000399713.6 link	c.*8C>A		downstream_gene_variant		5		ENSP00000408616.1	C9JMP5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000122

AC:

AN:

245846

Hom.:

AF XY:

0.00000750

AC XY:

AN XY:

133336

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000165

Gnomad SAS 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:

0.00000274

AC:

AN:

1461098

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726744

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.463C>A (p.L155M) alteration is located in exon 7 (coding exon 6) of the NABP2 gene. This alteration results from a C to A substitution at nucleotide position 463, causing the leucine (L) at amino acid position 155 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.027

T;T;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.61

.;.;T

M_CAP

Benign

0.0083

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.90

L;L;L

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.090

N;N;N

REVEL

Benign

0.079

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.23

T;T;T

Polyphen

0.99

D;D;D

Vest4

0.30

MutPred

0.21

Loss of catalytic residue at L155 (P = 0.0527);Loss of catalytic residue at L155 (P = 0.0527);Loss of catalytic residue at L155 (P = 0.0527);

MVP

0.63

MPC

0.90

ClinPred

0.24

GERP RS

5.4

Varity_R

0.093

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over