16-22534127-G-A

Position:

• chr16-22534127-G-A

Variant summary

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

The ENST00000424340.7(NPIPB5):​c.1144G>A​(p.Asp382Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 6)
  • Exomes 𝑓: 0.0000015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB5 ENST00000424340.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.960

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=0.16135621).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPIPB5	NM_001395849.1	c.1144G>A	p.Asp382Asn	missense_variant	7/7	ENST00000424340.7	NP_001382778.1
LOC105371131	XR_007065022.1	n.150+3351C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPIPB5	ENST00000424340.7	c.1144G>A	p.Asp382Asn	missense_variant	7/7	1	NM_001395849.1	ENSP00000440703	P1

Frequencies

GnomAD3 genomes Cov.: 6

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000151 AC: 1 AN: 663686 Hom.: 0 Cov.: 8 AF XY: 0.00000283 AC XY: 1 AN XY: 352936

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000293

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 6

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2024

The c.1144G>A (p.D382N) alteration is located in exon 7 (coding exon 7) of the NPIPB5 gene. This alteration results from a G to A substitution at nucleotide position 1144, causing the aspartic acid (D) at amino acid position 382 to be replaced by an asparagine (N). 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	0.32
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	.;.;T;T;.;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.14	N
LIST_S2	Uncertain	0.87	.;D;T;.;D;.
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.16	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N
PROVEAN	Benign	-1.6	N;.;N;N;N;.
REVEL	Benign	0.055
Sift	Benign	0.31	T;.;D;D;T;.
Sift4G	Benign	0.37	T;T;T;T;T;T
Polyphen		0.99	.;.;D;D;.;.
Vest4		0.046, 0.048, 0.051, 0.055
MutPred		0.15		Loss of stability (P = 0.0799);Loss of stability (P = 0.0799);Loss of stability (P = 0.0799);Loss of stability (P = 0.0799);Loss of stability (P = 0.0799);.;
MVP		0.040
ClinPred		0.66	D
Varity_R		0.097
gMVP		0.0046

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: chr16-22545448;