Genetic Variant NABP2:p.Ser172Phe (chr12-56229092-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024068.4(NABP2):c.515C>T(p.Ser172Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.0 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NABP2
NM_024068.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.08

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11431205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NABP2	NM_024068.4 link	c.515C>T	p.Ser172Phe	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.515C>T	p.Ser172Phe	missense_variant	Exon 7 of 7	1	NM_024068.4	ENSP00000267023.4	Q9BQ15-1
NABP2	ENST00000380198.6 link	c.515C>T	p.Ser172Phe	missense_variant	Exon 6 of 6	1		ENSP00000369545.2	Q9BQ15-1
NABP2	ENST00000341463.5 link	c.515C>T	p.Ser172Phe	missense_variant	Exon 7 of 7	3		ENSP00000368862.3	Q9BQ15-1
NABP2	ENST00000399713.6 link	c.*60C>T		downstream_gene_variant		5		ENSP00000408616.1	C9JMP5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

144294

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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:

0.00000416

AC:

AN:

240500

Hom.:

AF XY:

0.00000761

AC XY:

AN XY:

131382

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000936

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000191

AC:

AN:

1097902

Hom.:

Cov.:

AF XY:

0.0000180

AC XY:

AN XY:

556914

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000125

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

144294

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69990

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.515C>T (p.S172F) alteration is located in exon 7 (coding exon 6) of the NABP2 gene. This alteration results from a C to T substitution at nucleotide position 515, causing the serine (S) at amino acid position 172 to be replaced by a phenylalanine (F). 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

0.15

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.052

T;T;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.73

.;.;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.028

Sift

Uncertain

0.0090

D;D;D

Sift4G

Uncertain

0.036

D;D;D

Polyphen

0.070

B;B;B

Vest4

0.27

MutPred

0.22

Loss of glycosylation at S172 (P = 3e-04);Loss of glycosylation at S172 (P = 3e-04);Loss of glycosylation at S172 (P = 3e-04);

MVP

0.24

MPC

0.91

ClinPred

0.26

GERP RS

5.2

Varity_R

0.10

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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