rs200248705

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-22533798-C-G
• chr16-22533798-C-A
• chr16-22533798-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001395849.1(NPIPB5):​c.815C>G​(p.Thr272Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 5)
  • Exomes 𝑓: 0.000089 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB5 NM_001395849.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.058073312).

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>G	p.Thr272Ser	missense	Exon 7 of 7	NP_001382778.1	A8MRT5
	NPIPB5	NM_001135865.3		c.815C>G	p.Thr272Ser	missense	Exon 9 of 9	NP_001129337.1	A8MRT5
	NPIPB5	NM_001395850.1		c.815C>G	p.Thr272Ser	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>G	p.Thr272Ser	missense	Exon 7 of 7	ENSP00000440703.1	A8MRT5
	NPIPB5	ENST00000528249.5	TSL:1	c.815C>G	p.Thr272Ser	missense	Exon 7 of 7	ENSP00000431553.1	E9PKP1
	NPIPB5	ENST00000517539.6	TSL:5	c.815C>G	p.Thr272Ser	missense	Exon 8 of 8	ENSP00000430633.1	A8MRT5

Frequencies

GnomAD3 genomes AF: 0.000290 AC: 7 AN: 24142 Hom.: 0 Cov.: 5

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000726

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000640 AC: 2 AN: 31262 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000153

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000894 AC: 42 AN: 469980 Hom.: 0 Cov.: 0 AF XY: 0.0000683 AC XY: 17 AN XY: 248940

⚠️ 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: 14104

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: 0.000137 AC: 38 AN: 276420

Other (OTH) AF: 0.0000743 AC: 2 AN: 26902

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.000290 AC: 7 AN: 24142 Hom.: 0 Cov.: 5 AF XY: 0.000261 AC XY: 3 AN XY: 11512

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

African (AFR) AF: 0.00 AC: 0 AN: 8900

American (AMR) AF: 0.00 AC: 0 AN: 2110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 652

East Asian (EAS) AF: 0.00 AC: 0 AN: 564

South Asian (SAS) AF: 0.00 AC: 0 AN: 564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 40

European-Non Finnish (NFE) AF: 0.000726 AC: 7 AN: 9644

Other (OTH) AF: 0.00 AC: 0 AN: 222

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000484472), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.065
DANN	Benign	0.52
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.00023	N
LIST_S2	Benign	0.072	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-0.99	T
PhyloP100		-4.4
PROVEAN	Benign	0.040	N
REVEL	Benign	0.079
Sift	Benign	0.43	T
Sift4G	Benign	0.45	T
Polyphen		0.047	B
Vest4		0.060
MutPred		0.37		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.014
ClinPred		0.050	T
Varity_R		0.082
gMVP		0.0096
Mutation Taster		=100/0	polymorphism

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;