NM_001267560.2:c.120T>C

Variant names:

• chr19-3728675-T-C
• rs142949186
• NM_001267560.2:c.120T>C

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.120T>C​(p.Ser40Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,613,808 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (5 hom.)
• Consequence: TJP3 NM_001267560.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -7.96
• 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=-0.93).
• BP6: Variant 19-3728675-T-C is Benign according to our data. Variant chr19-3728675-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2649006.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-7.96 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 5 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.120T>C	p.Ser40Ser	synonymous	Exon 3 of 21	NP_001254489.1	O95049-1
	TJP3	NM_001267561.2		c.147T>C	p.Ser49Ser	synonymous	Exon 3 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.120T>C	p.Ser40Ser	synonymous	Exon 3 of 21	ENSP00000439278.1	O95049-1
	TJP3	ENST00000587686.1	TSL:1	c.177T>C	p.Ser59Ser	synonymous	Exon 2 of 20	ENSP00000467864.1	O95049-3
	TJP3	ENST00000589378.5	TSL:2	c.147T>C	p.Ser49Ser	synonymous	Exon 3 of 21	ENSP00000465419.1	O95049-4

Frequencies

GnomAD3 genomes AF: 0.00152 AC: 232 AN: 152170 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00232

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00144 AC: 359 AN: 248886 AF XY: 0.00151

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.000348

Gnomad ASJ exome AF: 0.00192

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00344

Gnomad NFE exome AF: 0.00202

Gnomad OTH exome AF: 0.00150

GnomAD4 exome AF: 0.00117 AC: 1711 AN: 1461520 Hom.: 5 Cov.: 33 AF XY: 0.00117 AC XY: 854 AN XY: 726990

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.000403 AC: 18 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00154 AC: 40 AN: 26016

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000523 AC: 45 AN: 86114

European-Finnish (FIN) AF: 0.00350 AC: 187 AN: 53380

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00120 AC: 1332 AN: 1111974

Other (OTH) AF: 0.00142 AC: 86 AN: 60376

GnomAD4 genome AF: 0.00152 AC: 232 AN: 152288 Hom.: 0 Cov.: 33 AF XY: 0.00142 AC XY: 106 AN XY: 74454

African (AFR) AF: 0.000144 AC: 6 AN: 41560

American (AMR) AF: 0.00222 AC: 34 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3468

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

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00217 AC: 23 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00232 AC: 158 AN: 68024

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.00190 Hom.: 1

Bravo AF: 0.00117

Asia WGS AF: 0.000289 AC: 1 AN: 3476

EpiCase AF: 0.00142

EpiControl AF: 0.000652

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	-0.93
CADD	Benign	0.084
DANN	Benign	0.49
PhyloP100		-8.0
PromoterAI		-0.089	Neutral
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: rs142949186; hg19: chr19-3728673;