16-22534125-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001395849.1(NPIPB5):c.1142C>T(p.Ala381Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 6)
  • Exomes 𝑓: 0.0029 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB5 NM_001395849.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.82

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027052164).
• BP6: Variant 16-22534125-C-T is Benign according to our data. Variant chr16-22534125-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2345686.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPIPB5	NM_001395849.1	c.1142C>T	p.Ala381Val	missense_variant	7/7	ENST00000424340.7
LOC105371131	XR_007065022.1	n.150+3353G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPIPB5	ENST00000424340.7	c.1142C>T	p.Ala381Val	missense_variant	7/7	1	NM_001395849.1	P1

Frequencies

GnomAD3 genomes AF: 0.00126 AC: 53 AN: 42132 Hom.: 0 Cov.: 6

Gnomad AFR AF: 0.000238

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000784

Gnomad ASJ AF: 0.00172

Gnomad EAS AF: 0.00313

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00105

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00180

Gnomad OTH AF: 0.00727

GnomAD3 exomes AF: 0.00682 AC: 395 AN: 57932 Hom.: 3 AF XY: 0.00698 AC XY: 206 AN XY: 29522

Gnomad AFR exome AF: 0.000751

Gnomad AMR exome AF: 0.00211

Gnomad ASJ exome AF: 0.000577

Gnomad EAS exome AF: 0.0262

Gnomad SAS exome AF: 0.000967

Gnomad FIN exome AF: 0.0200

Gnomad NFE exome AF: 0.00636

Gnomad OTH exome AF: 0.00611

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00288 AC: 1949 AN: 676472 Hom.: 2 Cov.: 9 AF XY: 0.00265 AC XY: 950 AN XY: 359120

Gnomad4 AFR exome AF: 0.000310

Gnomad4 AMR exome AF: 0.000597

Gnomad4 ASJ exome AF: 0.000156

Gnomad4 EAS exome AF: 0.00134

Gnomad4 SAS exome AF: 0.000341

Gnomad4 FIN exome AF: 0.00784

Gnomad4 NFE exome AF: 0.00345

Gnomad4 OTH exome AF: 0.00259

GnomAD4 genome AF: 0.00126 AC: 53 AN: 42192 Hom.: 0 Cov.: 6 AF XY: 0.00123 AC XY: 25 AN XY: 20398

Gnomad4 AFR AF: 0.000237

Gnomad4 AMR AF: 0.000782

Gnomad4 ASJ AF: 0.00172

Gnomad4 EAS AF: 0.00314

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00105

Gnomad4 NFE AF: 0.00180

Gnomad4 OTH AF: 0.00719

Alfa AF: 0.00304 Hom.: 0

ExAC AF: 0.00262 AC: 44

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	11
Dann	Uncertain	0.99
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0087	N
MetaRNN	Benign	0.0027	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PROVEAN	Benign	-0.64	N;.;N;N;N;.
REVEL	Benign	0.12
Sift	Benign	0.31	T;.;T;T;T;.
Sift4G	Benign	0.46	T;T;T;T;T;T
Polyphen		0.42	.;.;B;B;.;.
Vest4		0.052, 0.048, 0.039
MutPred		0.13		Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);.;
MVP		0.014
ClinPred		0.028	T
Varity_R		0.042
gMVP		0.0077

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

LitVar

Other links and lift over

dbSNP: rs768212601; hg19: chr16-22545446; COSMIC: COSV69997133; COSMIC: COSV69997133;