chr10-68288973-T-A

Variant names:

• chr10-68288973-T-A
• rs2044323163
• NM_022129.4:c.470A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022129.4(PBLD):​c.470A>T​(p.Asp157Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/22 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)
• Consequence: PBLD NM_022129.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.07
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PBLD	NM_022129.4	c.470A>T	p.Asp157Val	missense_variant	Exon 7 of 10	ENST00000358769.7	NP_071412.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBLD	ENST00000358769.7	c.470A>T	p.Asp157Val	missense_variant	Exon 7 of 10	5	NM_022129.4	ENSP00000351619.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.470A>T (p.D157V) alteration is located in exon 7 (coding exon 6) of the PBLD gene. This alteration results from a A to T substitution at nucleotide position 470, causing the aspartic acid (D) at amino acid position 157 to be replaced by a valine (V). 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	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.029	T;T;T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.012
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.88	D;D;.;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.61	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	.;L;L;L
PhyloP100		1.1
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.4	N;D;D;.
REVEL	Benign	0.12
Sift	Benign	0.042	D;T;T;.
Sift4G	Benign	0.25	T;T;T;T
Polyphen		0.097	.;B;B;.
Vest4		0.60
MutPred		0.64		.;Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);
MVP		0.32
MPC		0.25
ClinPred		0.40	T
GERP RS		5.3
PromoterAI		-0.010	Neutral
Varity_R		0.48
gMVP		0.75
Mutation Taster		=89/11	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: rs2044323163; hg19: chr10-70048730;