Variant 1-206937308-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000356495.5(PIGR):c.832A>T(p.Asn278Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,461,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

PIGR
ENST00000356495.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.13

Variant links:

Genes affected

PIGR (HGNC:8968): (polymeric immunoglobulin receptor) This gene is a member of the immunoglobulin superfamily. The encoded poly-Ig receptor binds polymeric immunoglobulin molecules at the basolateral surface of epithelial cells; the complex is then transported across the cell to be secreted at the apical surface. A significant association was found between immunoglobulin A nephropathy and several SNPs in this gene.[provided by RefSeq, Sep 2009]

PIGR links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20959872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGR	NM_002644.4 linkuse as main transcript	c.832A>T	p.Asn278Tyr	missense_variant	4/11	ENST00000356495.5	NP_002635.2
PIGR	XM_011509629.2 linkuse as main transcript	c.832A>T	p.Asn278Tyr	missense_variant	4/11		XP_011507931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGR	ENST00000356495.5 linkuse as main transcript	c.832A>T	p.Asn278Tyr	missense_variant	4/11	1	NM_002644.4	ENSP00000348888	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250374

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135306

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1461076

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726766

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2024

The c.832A>T (p.N278Y) alteration is located in exon 4 (coding exon 3) of the PIGR gene. This alteration results from a A to T substitution at nucleotide position 832, causing the asparagine (N) at amino acid position 278 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.57

CADD

Benign

4.9

DANN

Benign

0.93

DEOGEN2

Benign

0.24

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.30

M_CAP

Benign

0.040

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.90

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.12

Sift

Uncertain

0.025

Sift4G

Uncertain

0.011

Polyphen

0.90

Vest4

0.18

MutPred

0.40

Gain of phosphorylation at N278 (P = 0.0388);

MVP

0.10

MPC

0.51

ClinPred

0.34

GERP RS

0.68

Varity_R

0.073

gMVP

0.32

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over