rs759057080

Variant names:

• chr12-56229094-C-A
• rs759057080
• NM_024068.4:c.517C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-56229094-C-A
• chr12-56229094-C-T

Variant summary

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

The NM_024068.4(NABP2):​c.517C>A​(p.His173Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000726 in 1,377,120 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. H173L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: NABP2 NM_024068.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.58
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024068.4. 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
	NABP2	NM_024068.4	MANE Select	c.517C>A	p.His173Asn	missense	Exon 7 of 7	NP_076973.1	Q9BQ15-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NABP2	ENST00000267023.9	TSL:1 MANE Select	c.517C>A	p.His173Asn	missense	Exon 7 of 7	ENSP00000267023.4	Q9BQ15-1
	NABP2	ENST00000380198.6	TSL:1	c.517C>A	p.His173Asn	missense	Exon 6 of 6	ENSP00000369545.2	Q9BQ15-1
	NABP2	ENST00000341463.5	TSL:3	c.517C>A	p.His173Asn	missense	Exon 7 of 7	ENSP00000368862.3	Q9BQ15-1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1377120 Hom.: 0 Cov.: 43 AF XY: 0.00000145 AC XY: 1 AN XY: 687990

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31724

American (AMR) AF: 0.00 AC: 0 AN: 44406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25488

East Asian (EAS) AF: 0.00 AC: 0 AN: 39076

South Asian (SAS) AF: 0.00 AC: 0 AN: 84304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5096

European-Non Finnish (NFE) AF: 9.63e-7 AC: 1 AN: 1038198

Other (OTH) AF: 0.00 AC: 0 AN: 57492

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 29

ExAC AF: 0.0000412 AC: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		4.6
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.12
Sift	Benign	0.35	T
Sift4G	Benign	0.47	T
Polyphen		0.85	P
Vest4		0.55
MutPred		0.18		Gain of relative solvent accessibility (P = 0.0098)
MVP		0.66
MPC		1.9
ClinPred		0.66	D
GERP RS		5.2
Varity_R		0.13
gMVP		0.37
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs759057080; hg19: chr12-56622878; COSMIC: COSV99907479; COSMIC: COSV99907479;