NM_001395849.1:c.1007A>G

Variant names:

• chr16-22533990-A-G
• NM_001395849.1:c.1007A>G

Variant summary

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

The NM_001395849.1(NPIPB5):​c.1007A>G​(p.Asp336Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 15)
  • Exomes 𝑓: 0.0000057 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB5 NM_001395849.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.946

Genes affected

NPIPB5 (HGNC:37233): (nuclear pore complex interacting protein family member B5) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LOC105371131 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21927309).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPIPB5	NM_001395849.1	c.1007A>G	p.Asp336Gly	missense_variant	Exon 7 of 7	ENST00000424340.7	NP_001382778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPIPB5	ENST00000424340.7	c.1007A>G	p.Asp336Gly	missense_variant	Exon 7 of 7	1	NM_001395849.1	ENSP00000440703.1

Frequencies

GnomAD3 genomes Cov.: 15

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000570 AC: 8 AN: 1404654 Hom.: 0 Cov.: 32 AF XY: 0.00000571 AC XY: 4 AN XY: 700732

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: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000652

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 15

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1007A>G (p.D336G) alteration is located in exon 7 (coding exon 7) of the NPIPB5 gene. This alteration results from a A to G substitution at nucleotide position 1007, causing the aspartic acid (D) at amino acid position 336 to be replaced by a glycine (G). 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	Uncertain	0.48
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	.;.;T;T;.;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.81	.;T;T;.;D;.
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.22	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Uncertain	-3.1	D;.;D;D;D;.
REVEL	Benign	0.048
Sift	Benign	0.11	T;.;D;D;T;.
Sift4G	Benign	0.21	T;T;T;T;T;T
Polyphen		0.98	.;.;D;D;.;.
Vest4		0.064, 0.063, 0.061, 0.070
MutPred		0.48		Loss of stability (P = 0.0326);Loss of stability (P = 0.0326);Loss of stability (P = 0.0326);Loss of stability (P = 0.0326);Loss of stability (P = 0.0326);.;
MVP		0.081
ClinPred		0.84	D
Varity_R		0.12
gMVP		0.0091

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: chr16-22545311;