Variant 10-68292153-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_022129.4(PBLD):c.369G>C(p.Leu123Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000851 in 1,613,910 control chromosomes in the GnomAD database, including 3 homozygotes. 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: 𝑓 0.00062 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00088 ( 2 hom. )

Consequence

PBLD
NM_022129.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.672

Variant links:

Genes affected

PBLD (HGNC:23301): (phenazine biosynthesis like protein domain containing) Enables identical protein binding activity. Involved in maintenance of gastrointestinal epithelium; negative regulation of SMAD protein signal transduction; and negative regulation of transforming growth factor beta receptor signaling pathway. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PBLD links:

PBLD (HGNC:):

PBLD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01686433).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PBLD	NM_022129.4 linkuse as main transcript	c.369G>C	p.Leu123Phe	missense_variant	5/10	ENST00000358769.7	NP_071412.2	P30039-1A0A024QZK5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PBLD	ENST00000358769.7 linkuse as main transcript	c.369G>C	p.Leu123Phe	missense_variant	5/10	5	NM_022129.4	ENSP00000351619.2		P30039-1

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000926

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000625

AC:

157

AN:

251106

Hom.:

AF XY:

0.000634

AC XY:

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000604

Gnomad NFE exome

AF:

0.00104

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000875

AC:

1279

AN:

1461640

Hom.:

Cov.:

AF XY:

0.000828

AC XY:

602

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000604

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000431

Gnomad4 NFE exome

AF:

0.00108

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.000617

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000926

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000691

Hom.:

Bravo

AF:

0.000688

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000651

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000948

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

Feb 13, 2024

The c.369G>C (p.L123F) alteration is located in exon 5 (coding exon 4) of the PBLD gene. This alteration results from a G to C substitution at nucleotide position 369, causing the leucine (L) at amino acid position 123 to be replaced by a phenylalanine (F). 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

0.15

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.071

DANN

Benign

0.13

DEOGEN2

Benign

0.046

T;T;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.093

LIST_S2

Benign

0.73

T;T;.;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.017

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.0

.;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

0.91

N;N;N;.

REVEL

Benign

0.086

Sift

Benign

0.92

T;T;T;.

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0010

.;B;B;.

Vest4

0.11

MutPred

0.64

.;Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);

MVP

0.040

MPC

0.20

ClinPred

0.0049

GERP RS

-7.3

Varity_R

0.063

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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