NM_001267560.2:c.414C>T

Variant names:

• chr19-3730507-C-T
• rs199667693
• NM_001267560.2:c.414C>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.414C>T​(p.Ser138Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000431 in 1,588,144 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00043 (6 hom.)
• Consequence: TJP3 NM_001267560.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -7.54
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 19-3730507-C-T is Benign according to our data. Variant chr19-3730507-C-T is described in ClinVar as Benign. ClinVar VariationId is 718463.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-7.54 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 6 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.414C>T	p.Ser138Ser	synonymous	Exon 5 of 21	NP_001254489.1	O95049-1
	TJP3	NM_001267561.2		c.441C>T	p.Ser147Ser	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.414C>T	p.Ser138Ser	synonymous	Exon 5 of 21	ENSP00000439278.1	O95049-1
	TJP3	ENST00000587686.1	TSL:1	c.471C>T	p.Ser157Ser	synonymous	Exon 4 of 20	ENSP00000467864.1	O95049-3
	TJP3	ENST00000589378.5	TSL:2	c.441C>T	p.Ser147Ser	synonymous	Exon 5 of 21	ENSP00000465419.1	O95049-4

Frequencies

GnomAD3 genomes AF: 0.000447 AC: 68 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00127 AC: 256 AN: 201186 AF XY: 0.00113

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000322

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0129

Gnomad FIN exome AF: 0.000681

Gnomad NFE exome AF: 0.000117

Gnomad OTH exome AF: 0.000382

GnomAD4 exome AF: 0.000430 AC: 617 AN: 1435830 Hom.: 6 Cov.: 32 AF XY: 0.000425 AC XY: 303 AN XY: 712818

African (AFR) AF: 0.00 AC: 0 AN: 32976

American (AMR) AF: 0.000238 AC: 10 AN: 41968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25684

East Asian (EAS) AF: 0.0107 AC: 414 AN: 38802

South Asian (SAS) AF: 0.000865 AC: 73 AN: 84358

European-Finnish (FIN) AF: 0.000660 AC: 31 AN: 46964

Middle Eastern (MID) AF: 0.000200 AC: 1 AN: 5004

European-Non Finnish (NFE) AF: 0.0000572 AC: 63 AN: 1100800

Other (OTH) AF: 0.000422 AC: 25 AN: 59274

GnomAD4 genome AF: 0.000446 AC: 68 AN: 152314 Hom.: 0 Cov.: 32 AF XY: 0.000470 AC XY: 35 AN XY: 74478

African (AFR) AF: 0.00 AC: 0 AN: 41570

American (AMR) AF: 0.0000653 AC: 1 AN: 15306

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

East Asian (EAS) AF: 0.0105 AC: 54 AN: 5160

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4830

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10630

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68024

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.0000693 Hom.: 0

Bravo AF: 0.000627

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.60
CADD	Benign	0.014
DANN	Benign	0.85
PhyloP100		-7.5
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: rs199667693; hg19: chr19-3730505;