rs1059177

Variant names:

• chr16-14765236-T-C
• rs1059177
• NM_001395485.2:c.933T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001395485.2(NPIPA2):​c.933T>C​(p.Cys311Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 18)
  • Exomes 𝑓: 0.00029 (8 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPA2 NM_001395485.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• Publications: 1 publications found

Genes affected

NPIPA2 (HGNC:41979): (nuclear pore complex interacting protein family member A2) Predicted to be involved in mRNA transport and protein transport. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP7: Synonymous conserved (PhyloP=-2.22 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395485.2. 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
	NPIPA2	NM_001395485.2	MANE Select	c.933T>C	p.Cys311Cys	synonymous	Exon 10 of 10	NP_001382414.1
	NPIPA2	NM_001395486.2		c.933T>C	p.Cys311Cys	synonymous	Exon 10 of 10	NP_001382415.1
	NPIPA2	NM_001277324.3		c.876T>C	p.Cys292Cys	synonymous	Exon 12 of 12	NP_001264253.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPIPA2	ENST00000529166.6	TSL:5 MANE Select	c.933T>C	p.Cys311Cys	synonymous	Exon 10 of 10	ENSP00000432029.1
	NPIPA2	ENST00000553201.1	TSL:1	c.876T>C	p.Cys292Cys	synonymous	Exon 8 of 8	ENSP00000446882.1
	NPIPA2	ENST00000891286.1		c.933T>C	p.Cys311Cys	synonymous	Exon 10 of 10	ENSP00000561345.1

Frequencies

GnomAD3 genomes AF: 0.00202 AC: 249 AN: 123100 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.00643

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00107

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: 0.0000185

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000827 AC: 50 AN: 60458 AF XY: 0.000609

Gnomad AFR exome AF: 0.00783

Gnomad AMR exome AF: 0.000365

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: 0.000504

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000288 AC: 398 AN: 1381774 Hom.: 8 Cov.: 28 AF XY: 0.000243 AC XY: 168 AN XY: 690808

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

African (AFR) AF: 0.00856 AC: 279 AN: 32594

American (AMR) AF: 0.000877 AC: 39 AN: 44484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25546

East Asian (EAS) AF: 0.00 AC: 0 AN: 39328

South Asian (SAS) AF: 0.0000704 AC: 6 AN: 85266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39344

Middle Eastern (MID) AF: 0.000249 AC: 1 AN: 4016

European-Non Finnish (NFE) AF: 0.0000123 AC: 13 AN: 1053014

Other (OTH) AF: 0.00103 AC: 60 AN: 58182

⚠️ 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: 0.00204 AC: 251 AN: 123188 Hom.: 0 Cov.: 18 AF XY: 0.00202 AC XY: 120 AN XY: 59394

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

African (AFR) AF: 0.00647 AC: 237 AN: 36628

American (AMR) AF: 0.00107 AC: 13 AN: 12170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2826

East Asian (EAS) AF: 0.00 AC: 0 AN: 4396

South Asian (SAS) AF: 0.00 AC: 0 AN: 3476

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 208

European-Non Finnish (NFE) AF: 0.0000185 AC: 1 AN: 54150

Other (OTH) AF: 0.00 AC: 0 AN: 1650

⚠️ 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: 0.00341 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.4
DANN	Benign	0.32
PhyloP100		-2.2
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: rs1059177; hg19: chr16-14859093;