Variant 1-206935726-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000356495.5(PIGR):c.1138A>G(p.Ser380Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000469 in 1,614,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S380N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00049 ( 0 hom. )

Consequence

PIGR
ENST00000356495.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0510

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039024174).

BP6

Variant 1-206935726-T-C is Benign according to our data. Variant chr1-206935726-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2639866.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGR	NM_002644.4 linkuse as main transcript	c.1138A>G	p.Ser380Gly	missense_variant	5/11	ENST00000356495.5	NP_002635.2
PIGR	XM_011509629.2 linkuse as main transcript	c.1138A>G	p.Ser380Gly	missense_variant	5/11		XP_011507931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGR	ENST00000356495.5 linkuse as main transcript	c.1138A>G	p.Ser380Gly	missense_variant	5/11	1	NM_002644.4	ENSP00000348888	P1

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.000559

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000458

AC:

114

AN:

248842

Hom.:

AF XY:

0.000401

AC XY:

AN XY:

134734

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000872

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000485

AC:

709

AN:

1461818

Hom.:

Cov.:

AF XY:

0.000454

AC XY:

330

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.000585

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.000315

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000594

Hom.:

Bravo

AF:

0.000355

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000560

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000711

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

PIGR: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.31

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.57

M_CAP

Benign

0.0056

MetaRNN

Benign

0.039

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.1

REVEL

Benign

0.046

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.0070

Polyphen

0.96

Vest4

0.082

MVP

0.12

MPC

0.31

ClinPred

0.068

GERP RS

0.35

Varity_R

0.28

gMVP

0.90

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