chr10-68288632-G-T

Variant names:

• chr10-68288632-G-T
• rs776720427
• NM_022129.4:c.542C>A

Variant summary

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

The NM_022129.4(PBLD):​c.542C>A​(p.Thr181Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T181M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PBLD NM_022129.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.36
• 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.542C>A	p.Thr181Lys	missense_variant	Exon 8 of 10	ENST00000358769.7	NP_071412.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBLD	ENST00000358769.7	c.542C>A	p.Thr181Lys	missense_variant	Exon 8 of 10	5	NM_022129.4	ENSP00000351619.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461834 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727208

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T;T;T;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.75	T;T;.;T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.46	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.3	.;M;M;M
PhyloP100		7.4
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.1	N;N;N;.
REVEL	Benign	0.17
Sift	Benign	0.086	T;T;T;.
Sift4G	Benign	0.36	T;T;T;T
Polyphen		0.88	.;P;P;.
Vest4		0.47
MutPred		0.63		.;Gain of loop (P = 0.0097);Gain of loop (P = 0.0097);Gain of loop (P = 0.0097);
MVP		0.33
MPC		0.39
ClinPred		0.92	D
GERP RS		4.9
PromoterAI		0.014	Neutral
Varity_R		0.45
gMVP		0.56
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs776720427; hg19: chr10-70048389;