16-22533798-C-T

Variant names:

• chr16-22533798-C-T
• rs200248705
• NM_001395849.1:c.815C>T

Variant summary

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

The NM_001395849.1(NPIPB5):​c.815C>T​(p.Thr272Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 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. T272S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 5)
  • Exomes 𝑓: 0.0000043 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB5 NM_001395849.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.42
• 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=0.08933687).

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.815C>T	p.Thr272Ile	missense	Exon 7 of 7	NP_001382778.1	A8MRT5
	NPIPB5	NM_001135865.3		c.815C>T	p.Thr272Ile	missense	Exon 9 of 9	NP_001129337.1	A8MRT5
	NPIPB5	NM_001395850.1		c.815C>T	p.Thr272Ile	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.815C>T	p.Thr272Ile	missense	Exon 7 of 7	ENSP00000440703.1	A8MRT5
	NPIPB5	ENST00000528249.5	TSL:1	c.815C>T	p.Thr272Ile	missense	Exon 7 of 7	ENSP00000431553.1	E9PKP1
	NPIPB5	ENST00000517539.6	TSL:5	c.815C>T	p.Thr272Ile	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: 0.00000426 AC: 2 AN: 470000 Hom.: 0 Cov.: 0 AF XY: 0.00000402 AC XY: 1 AN XY: 248950

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 14106

American (AMR) AF: 0.0000802 AC: 2 AN: 24928

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14878

East Asian (EAS) AF: 0.00 AC: 0 AN: 31082

South Asian (SAS) AF: 0.00 AC: 0 AN: 49764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29852

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2050

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 276436

Other (OTH) AF: 0.00 AC: 0 AN: 26904

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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	Uncertain	0.45
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.5
DANN	Benign	0.87
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00028	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.0	T
PhyloP100		-4.4
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.072
Sift	Benign	0.39	T
Sift4G	Benign	0.40	T
Polyphen		0.62	P
Vest4		0.096
MutPred		0.41		Loss of glycosylation at T272 (P = 0.0065)
MVP		0.040
ClinPred		0.13	T
Varity_R		0.045
gMVP		0.015

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: rs200248705; hg19: chr16-22545119;