rs755632125

Variant names:

• chr16-22534471-C-T
• rs755632125
• NM_001395849.1:c.1488C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The ENST00000424340.7(NPIPB5):​c.1488C>T​(p.Ala496Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 20)
  • Exomes 𝑓: 0.000034 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB5 ENST00000424340.7 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.105
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 16-22534471-C-T is Benign according to our data. Variant chr16-22534471-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 403260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.105 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000424340.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPIPB5	NM_001395849.1	MANE Select	c.1488C>T	p.Ala496Ala	synonymous	Exon 7 of 7	NP_001382778.1
	NPIPB5	NM_001135865.3		c.1488C>T	p.Ala496Ala	synonymous	Exon 9 of 9	NP_001129337.1
	NPIPB5	NM_001395850.1		c.1488C>T	p.Ala496Ala	synonymous	Exon 8 of 8	NP_001382779.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPIPB5	ENST00000424340.7	TSL:1 MANE Select	c.1488C>T	p.Ala496Ala	synonymous	Exon 7 of 7	ENSP00000440703.1
	NPIPB5	ENST00000528249.5	TSL:1	c.1488C>T	p.Ala496Ala	synonymous	Exon 7 of 7	ENSP00000431553.1
	NPIPB5	ENST00000517539.6	TSL:5	c.1488C>T	p.Ala496Ala	synonymous	Exon 8 of 8	ENSP00000430633.1

Frequencies

GnomAD3 genomes AF: 0.000272 AC: 32 AN: 117504 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.000233

Gnomad AMI AF: 0.00154

Gnomad AMR AF: 0.0000852

Gnomad ASJ AF: 0.000342

Gnomad EAS AF: 0.000311

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000133

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000266

Gnomad OTH AF: 0.000635

GnomAD2 exomes AF: 0.00 AC: 0 AN: 220736 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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000339 AC: 28 AN: 826670 Hom.: 0 Cov.: 19 AF XY: 0.0000439 AC XY: 19 AN XY: 432852

⚠️ 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: 21452

American (AMR) AF: 0.0000251 AC: 1 AN: 39782

Ashkenazi Jewish (ASJ) AF: 0.0000480 AC: 1 AN: 20814

East Asian (EAS) AF: 0.00 AC: 0 AN: 35326

South Asian (SAS) AF: 0.000211 AC: 15 AN: 71086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47792

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2828

European-Non Finnish (NFE) AF: 0.0000146 AC: 8 AN: 548952

Other (OTH) AF: 0.0000776 AC: 3 AN: 38638

⚠️ 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 AF: 0.000272 AC: 32 AN: 117592 Hom.: 0 Cov.: 20 AF XY: 0.000297 AC XY: 17 AN XY: 57204

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

African (AFR) AF: 0.000232 AC: 7 AN: 30160

American (AMR) AF: 0.0000851 AC: 1 AN: 11750

Ashkenazi Jewish (ASJ) AF: 0.000342 AC: 1 AN: 2926

East Asian (EAS) AF: 0.000311 AC: 1 AN: 3220

South Asian (SAS) AF: 0.00123 AC: 4 AN: 3242

European-Finnish (FIN) AF: 0.000133 AC: 1 AN: 7532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 164

European-Non Finnish (NFE) AF: 0.000266 AC: 15 AN: 56370

Other (OTH) AF: 0.000634 AC: 1 AN: 1578

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000843 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.71
PhyloP100		0.10
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: rs755632125; hg19: chr16-22545792; COSMIC: COSV69995071; COSMIC: COSV69995071;