NM_001267560.2:c.1500C>T

Variant names:

• chr19-3739003-C-T
• rs56138006
• NM_001267560.2:c.1500C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001267560.2(TJP3):​c.1500C>T​(p.Asp500Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,613,096 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (14 hom.)
• Consequence: TJP3 NM_001267560.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.950
• Publications: 1 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 19-3739003-C-T is Benign according to our data. Variant chr19-3739003-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2649008.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.95 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.1500C>T	p.Asp500Asp	synonymous	Exon 13 of 21	NP_001254489.1	O95049-1
	TJP3	NM_001267561.2		c.1527C>T	p.Asp509Asp	synonymous	Exon 13 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.1500C>T	p.Asp500Asp	synonymous	Exon 13 of 21	ENSP00000439278.1	O95049-1
	TJP3	ENST00000587686.1	TSL:1	c.1557C>T	p.Asp519Asp	synonymous	Exon 12 of 20	ENSP00000467864.1	O95049-3
	TJP3	ENST00000589378.5	TSL:2	c.1527C>T	p.Asp509Asp	synonymous	Exon 13 of 21	ENSP00000465419.1	O95049-4

Frequencies

GnomAD3 genomes AF: 0.00240 AC: 365 AN: 152238 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000989

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00340

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00372

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00187 AC: 468 AN: 250052 AF XY: 0.00180

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00194

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.000648

Gnomad NFE exome AF: 0.00300

Gnomad OTH exome AF: 0.00312

GnomAD4 exome AF: 0.00324 AC: 4732 AN: 1460740 Hom.: 14 Cov.: 33 AF XY: 0.00310 AC XY: 2254 AN XY: 726672

African (AFR) AF: 0.000807 AC: 27 AN: 33476

American (AMR) AF: 0.00199 AC: 89 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26124

East Asian (EAS) AF: 0.000328 AC: 13 AN: 39694

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86196

European-Finnish (FIN) AF: 0.000551 AC: 29 AN: 52632

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5760

European-Non Finnish (NFE) AF: 0.00392 AC: 4362 AN: 1111798

Other (OTH) AF: 0.00326 AC: 197 AN: 60366

GnomAD4 genome AF: 0.00240 AC: 365 AN: 152356 Hom.: 2 Cov.: 33 AF XY: 0.00230 AC XY: 171 AN XY: 74504

African (AFR) AF: 0.000986 AC: 41 AN: 41588

American (AMR) AF: 0.00340 AC: 52 AN: 15302

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

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00372 AC: 253 AN: 68032

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00284 Hom.: 1

Bravo AF: 0.00262

Asia WGS AF: 0.000289 AC: 2 AN: 3478

EpiCase AF: 0.00322

EpiControl AF: 0.00344

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	-0.35
CADD	Benign	0.97
DANN	Benign	0.73
PhyloP100		-0.95
Mutation Taster		=100/0	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: rs56138006; hg19: chr19-3739001;