chr2-191685745-C-T

Variant names:

• chr2-191685745-C-T
• NM_001031716.5:c.592C>T

Variant summary

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

The NM_001031716.5(NABP1):​c.592C>T​(p.Pro198Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,764 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NABP1 NM_001031716.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.52
• Publications: 0 publications found

Genes affected

NABP1 (HGNC:26232): (nucleic acid binding protein 1) Single-stranded DNA (ssDNA)-binding proteins, such as OBFC2A, 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_001031716.5. 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
	NABP1	NM_001031716.5	MANE Select	c.592C>T	p.Pro198Ser	missense	Exon 6 of 6	NP_001026886.1	Q96AH0-1
	NABP1	NM_001254736.3		c.352C>T	p.Pro118Ser	missense	Exon 6 of 6	NP_001241665.1	Q96AH0-2
	NABP1	NR_045622.3		n.711C>T		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NABP1	ENST00000425611.9	TSL:1 MANE Select	c.592C>T	p.Pro198Ser	missense	Exon 6 of 6	ENSP00000403683.2	Q96AH0-1
	NABP1	ENST00000410026.7	TSL:1	c.352C>T	p.Pro118Ser	missense	Exon 6 of 6	ENSP00000387243.1	Q96AH0-2
	NABP1	ENST00000970387.1		c.586C>T	p.Pro196Ser	missense	Exon 6 of 6	ENSP00000640446.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461764 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727174

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111952

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

GnomAD4 genome Cov.: 32

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	Benign	0.25
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0087	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.5
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.19
Sift	Benign	0.066	T
Sift4G	Benign	0.38	T
Polyphen		1.0	D
Vest4		0.65
MutPred		0.30		Gain of phosphorylation at P198 (P = 0.0079)
MVP		0.78
MPC		0.20
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.37
gMVP		0.50
Mutation Taster		=56/44	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

hg19: chr2-192550471;