19-3730627-C-T

Variant names:

• chr19-3730627-C-T
• rs151121292
• NM_001267560.2:c.534C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001267560.2(TJP3):​c.534C>T​(p.Ser178Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000354 in 1,611,852 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (2 hom.)
• Consequence: TJP3 NM_001267560.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.20
• Publications: 0 publications found

Genes affected

TJP3 (HGNC:11829): (tight junction protein 3) The protein encoded by this gene is a member of the membrane-associated guanylate kinase-like (MAGUK) protein family which is characterized by members having multiple PDZ domains, a single SH3 domain, and a single guanylate kinase-like (GUK)-domain. In addition, members of the zonula occludens protein subfamily have an acidic domain, a basic arginine-rich region, and a proline-rich domain. The protein encoded by this gene plays a role in the linkage between the actin cytoskeleton and tight-junctions and also sequesters cyclin D1 at tight junctions during mitosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms. This gene has a partial pseudogene on chromosome 1. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 19-3730627-C-T is Benign according to our data. Variant chr19-3730627-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2649007.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-6.2 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001267560.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TJP3	NM_001267560.2	MANE Select	c.534C>T	p.Ser178Ser	synonymous	Exon 5 of 21	NP_001254489.1	O95049-1
	TJP3	NM_001267561.2		c.561C>T	p.Ser187Ser	synonymous	Exon 5 of 21	NP_001254490.1	O95049-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TJP3	ENST00000541714.7	TSL:2 MANE Select	c.534C>T	p.Ser178Ser	synonymous	Exon 5 of 21	ENSP00000439278.1	O95049-1
	TJP3	ENST00000587686.1	TSL:1	c.591C>T	p.Ser197Ser	synonymous	Exon 4 of 20	ENSP00000467864.1	O95049-3
	TJP3	ENST00000589378.5	TSL:2	c.561C>T	p.Ser187Ser	synonymous	Exon 5 of 21	ENSP00000465419.1	O95049-4

Frequencies

GnomAD3 genomes AF: 0.00166 AC: 252 AN: 152194 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00562

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

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: 0.00191

GnomAD2 exomes AF: 0.000467 AC: 114 AN: 243860 AF XY: 0.000330

Gnomad AFR exome AF: 0.00600

Gnomad AMR exome AF: 0.000521

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000920

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000215 AC: 314 AN: 1459540 Hom.: 2 Cov.: 32 AF XY: 0.000180 AC XY: 131 AN XY: 726216

African (AFR) AF: 0.00681 AC: 228 AN: 33476

American (AMR) AF: 0.000492 AC: 22 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86254

European-Finnish (FIN) AF: 0.0000390 AC: 2 AN: 51232

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.0000315 AC: 35 AN: 1111918

Other (OTH) AF: 0.000381 AC: 23 AN: 60358

GnomAD4 genome AF: 0.00168 AC: 256 AN: 152312 Hom.: 2 Cov.: 32 AF XY: 0.00156 AC XY: 116 AN XY: 74488

African (AFR) AF: 0.00570 AC: 237 AN: 41574

American (AMR) AF: 0.000981 AC: 15 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.000743 Hom.: 0

Bravo AF: 0.00199

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.24
DANN	Benign	0.80
PhyloP100		-6.2
Mutation Taster		=100/0	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: rs151121292; hg19: chr19-3730625;