2-191685745-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NABP1	NM_001031716.5	c.592C>T	p.Pro198Ser	missense_variant	Exon 6 of 6	ENST00000425611.9	NP_001026886.1
NABP1	NM_001254736.3	c.352C>T	p.Pro118Ser	missense_variant	Exon 6 of 6		NP_001241665.1
NABP1	NR_045622.3	n.711C>T		non_coding_transcript_exon_variant	Exon 7 of 7
NABP1	NR_045623.3	n.1175C>T		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NABP1	ENST00000425611.9	c.592C>T	p.Pro198Ser	missense_variant	Exon 6 of 6	1	NM_001031716.5	ENSP00000403683.2

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

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.592C>T (p.P198S) alteration is located in exon 6 (coding exon 6) of the NABP1 gene. This alteration results from a C to T substitution at nucleotide position 592, causing the proline (P) at amino acid position 198 to be replaced by a serine (S). 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	0.25
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;T
M_CAP	Benign	0.0087	T
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.5	.;.;M
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Benign	0.19
Sift	Benign	0.066	T;T;T
Sift4G	Benign	0.38	T;T;T
Polyphen		1.0	D;D;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-192550471;