rs761230580

Variant names:

• chr10-68284236-C-G
• rs761230580
• NM_022129.4:c.808G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-68284236-C-G
• chr10-68284236-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_022129.4(PBLD):​c.808G>C​(p.Gly270Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: PBLD NM_022129.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.62
• Publications: 2 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3855643).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PBLD	NM_022129.4	c.808G>C	p.Gly270Arg	missense_variant	Exon 10 of 10	ENST00000358769.7	NP_071412.2
PBLD	XM_005270028.5	c.808G>C	p.Gly270Arg	missense_variant	Exon 10 of 10		XP_005270085.1
PBLD	XM_011540060.4	c.783G>C	p.Thr261Thr	synonymous_variant	Exon 10 of 10		XP_011538362.1
PBLD	XM_017016513.2	c.783G>C	p.Thr261Thr	synonymous_variant	Exon 10 of 10		XP_016872002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBLD	ENST00000358769.7	c.808G>C	p.Gly270Arg	missense_variant	Exon 10 of 10	5	NM_022129.4	ENSP00000351619.2
PBLD	ENST00000309049.8	c.808G>C	p.Gly270Arg	missense_variant	Exon 10 of 10	1		ENSP00000308466.4
PBLD	ENST00000336578.5	c.709G>C	p.Gly237Arg	missense_variant	Exon 8 of 8	1		ENSP00000338041.1
PBLD	ENST00000468798.5	c.212-946G>C		intron_variant	Intron 2 of 2	3		ENSP00000476261.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152132 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000281 AC: 7 AN: 249054 AF XY: 0.0000297

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000539

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000152 AC: 222 AN: 1461806 Hom.: 0 Cov.: 31 AF XY: 0.000136 AC XY: 99 AN XY: 727202

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

American (AMR) AF: 0.00 AC: 0 AN: 44714

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

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

European-Non Finnish (NFE) AF: 0.000193 AC: 215 AN: 1111966

Other (OTH) AF: 0.000116 AC: 7 AN: 60392

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152132 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74288

African (AFR) AF: 0.0000241 AC: 1 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.073	T;T;T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.93	D;D;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	.;M;M
PhyloP100		2.6
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-4.4	D;D;D
REVEL	Benign	0.19
Sift	Uncertain	0.0030	D;D;D
Sift4G	Benign	0.13	T;T;T
Polyphen		0.57	.;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		0.80	D
GERP RS		4.0
Varity_R		0.38
gMVP		0.71
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs761230580; hg19: chr10-70043993;