rs28411392

Variant names:

• chr7-116210509-C-T
• rs28411392
• ENST00000937597.1:c.-199C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000937597.1(TES):​c.-199C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 468,394 control chromosomes in the GnomAD database, including 82,293 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.57 (25010 hom., cov: 34)
  • Exomes 𝑓: 0.59 (57283 hom.)
• Consequence: TES ENST00000937597.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.682
• Publications: 8 publications found

Genes affected

TES (HGNC:14620): (testin LIM domain protein) Cancer-associated chromosomal changes often involve regions containing fragile sites. This gene maps to a common fragile site on chromosome 7q31.2 designated FRA7G. This gene is similar to mouse Testin, a testosterone-responsive gene encoding a Sertoli cell secretory protein containing three LIM domains. LIM domains are double zinc-finger motifs that mediate protein-protein interactions between transcription factors, cytoskeletal proteins and signaling proteins. This protein is a negative regulator of cell growth and may act as a tumor suppressor. This scaffold protein may also play a role in cell adhesion, cell spreading and in the reorganization of the actin cytoskeleton. Multiple protein isoforms are encoded by transcript variants of this gene.[provided by RefSeq, Aug 2023]

ENSG00000279086 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000937597.1. 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
	TES	NM_015641.4	MANE Select	c.-199C>T		upstream_gene	N/A	NP_056456.1	A4D0U5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TES	ENST00000937597.1		c.-199C>T		5_prime_UTR	Exon 1 of 7	ENSP00000607656.1
	TES	ENST00000461440.5	TSL:2	n.4C>T		non_coding_transcript_exon	Exon 1 of 3
	ENSG00000279086	ENST00000624389.1	TSL:6	n.1003G>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86255 AN: 151806 Hom.: 24959 Cov.: 34

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.541

GnomAD4 exome AF: 0.594 AC: 187932 AN: 316480 Hom.: 57283 Cov.: 5 AF XY: 0.593 AC XY: 93598 AN XY: 157890

African (AFR) AF: 0.499 AC: 3634 AN: 7288

American (AMR) AF: 0.674 AC: 4003 AN: 5936

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 3959 AN: 7794

East Asian (EAS) AF: 0.879 AC: 17163 AN: 19520

South Asian (SAS) AF: 0.574 AC: 2385 AN: 4152

European-Finnish (FIN) AF: 0.572 AC: 18088 AN: 31648

Middle Eastern (MID) AF: 0.575 AC: 717 AN: 1248

European-Non Finnish (NFE) AF: 0.577 AC: 128296 AN: 222494

Other (OTH) AF: 0.591 AC: 9687 AN: 16400

GnomAD4 genome AF: 0.568 AC: 86357 AN: 151914 Hom.: 25010 Cov.: 34 AF XY: 0.575 AC XY: 42684 AN XY: 74262

African (AFR) AF: 0.495 AC: 20539 AN: 41478

American (AMR) AF: 0.636 AC: 9722 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1808 AN: 3472

East Asian (EAS) AF: 0.857 AC: 4387 AN: 5118

South Asian (SAS) AF: 0.597 AC: 2881 AN: 4826

European-Finnish (FIN) AF: 0.588 AC: 6188 AN: 10520

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.574 AC: 38990 AN: 67896

Other (OTH) AF: 0.545 AC: 1151 AN: 2110

Alfa AF: 0.573 Hom.: 3109

Bravo AF: 0.568

Asia WGS AF: 0.709 AC: 2440 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.91
PhyloP100		0.68
PromoterAI		0.18	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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: rs28411392; hg19: chr7-115850563;