chr16-22533744-A-G

Variant names:

• chr16-22533744-A-G
• rs2049882209
• NM_001395849.1:c.761A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001395849.1(NPIPB5):​c.761A>G​(p.His254Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. 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. H254P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 5)
  • Exomes 𝑓: 0.0000045 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB5 NM_001395849.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14669514).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395849.1. 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
	NPIPB5	NM_001395849.1	MANE Select	c.761A>G	p.His254Arg	missense	Exon 7 of 7	NP_001382778.1	A8MRT5
	NPIPB5	NM_001135865.3		c.761A>G	p.His254Arg	missense	Exon 9 of 9	NP_001129337.1	A8MRT5
	NPIPB5	NM_001395850.1		c.761A>G	p.His254Arg	missense	Exon 8 of 8	NP_001382779.1	A8MRT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPIPB5	ENST00000424340.7	TSL:1 MANE Select	c.761A>G	p.His254Arg	missense	Exon 7 of 7	ENSP00000440703.1	A8MRT5
	NPIPB5	ENST00000528249.5	TSL:1	c.761A>G	p.His254Arg	missense	Exon 7 of 7	ENSP00000431553.1	E9PKP1
	NPIPB5	ENST00000517539.6	TSL:5	c.761A>G	p.His254Arg	missense	Exon 8 of 8	ENSP00000430633.1	A8MRT5

Frequencies

GnomAD3 genomes Cov.: 5

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000448 AC: 2 AN: 446450 Hom.: 0 Cov.: 0 AF XY: 0.00000425 AC XY: 1 AN XY: 235460

African (AFR) AF: 0.00 AC: 0 AN: 12648

American (AMR) AF: 0.00 AC: 0 AN: 19110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13774

East Asian (EAS) AF: 0.00 AC: 0 AN: 30824

South Asian (SAS) AF: 0.00 AC: 0 AN: 46036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29154

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1954

European-Non Finnish (NFE) AF: 0.00000749 AC: 2 AN: 267036

Other (OTH) AF: 0.00 AC: 0 AN: 25914

GnomAD4 genome Cov.: 5

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.66
DANN	Benign	0.87
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00024	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.97	T
PhyloP100		-1.4
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.062
Sift	Benign	0.23	T
Sift4G	Benign	0.42	T
Polyphen		0.027	B
Vest4		0.10
MutPred		0.70		Gain of solvent accessibility (P = 0.0273)
MVP		0.030
ClinPred		0.089	T
Varity_R		0.11
gMVP		0.0083

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: rs2049882209; hg19: chr16-22545065;