10-68284236-C-T

Position:

chr10-68284236-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_022129.4(PBLD):c.808G>A(p.Gly270Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,613,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

PBLD
NM_022129.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.62

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4016136).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PBLD	NM_022129.4 linkuse as main transcript	c.808G>A	p.Gly270Arg	missense_variant	10/10	ENST00000358769.7	NP_071412.2	P30039-1A0A024QZK5
PBLD	XM_005270028.5 linkuse as main transcript	c.808G>A	p.Gly270Arg	missense_variant	10/10		XP_005270085.1	P30039-1A0A024QZK5
PBLD	XM_011540060.4 linkuse as main transcript	c.783G>A	p.Thr261Thr	synonymous_variant	10/10		XP_011538362.1
PBLD	XM_017016513.2 linkuse as main transcript	c.783G>A	p.Thr261Thr	synonymous_variant	10/10		XP_016872002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PBLD	ENST00000358769.7 linkuse as main transcript	c.808G>A	p.Gly270Arg	missense_variant	10/10	5	NM_022129.4	ENSP00000351619.2	P30039-1
PBLD	ENST00000309049.8 linkuse as main transcript	c.808G>A	p.Gly270Arg	missense_variant	10/10	1		ENSP00000308466.4	P30039-1
PBLD	ENST00000336578.5 linkuse as main transcript	c.709G>A	p.Gly237Arg	missense_variant	8/8	1		ENSP00000338041.1	A0A0C4DFS0
PBLD	ENST00000468798.5 linkuse as main transcript	c.212-946G>A		intron_variant		3		ENSP00000476261.1	V9GY00

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

249054

Hom.:

AF XY:

0.0000371

AC XY:

AN XY:

134818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000898

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000752

AC:

AN:

1461810

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000247

AC:

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 15, 2023

The c.808G>A (p.G270R) alteration is located in exon 10 (coding exon 9) of the PBLD gene. This alteration results from a G to A substitution at nucleotide position 808, causing the glycine (G) at amino acid position 270 to be replaced by an arginine (R). 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

0.25

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.073

T;T;T

Eigen

Benign

-0.095

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.93

D;D;.

M_CAP

Benign

0.013

MetaRNN

Benign

0.40

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

.;M;M

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-4.4

D;D;D

REVEL

Benign

0.21

Sift

Uncertain

0.0030

D;D;D

Sift4G

Benign

0.13

T;T;T

Polyphen

0.74

.;P;P

Vest4

0.41

MutPred

0.63

.;Gain of MoRF binding (P = 0.0358);Gain of MoRF binding (P = 0.0358);

MVP

0.37

MPC

0.72

ClinPred

0.89

GERP RS

4.0

Varity_R

0.38

gMVP

0.71

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