7-116210621-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015641.4(TES):c.-87C>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 0.293 in 1,257,408 control chromosomes in the GnomAD database, including 57,137 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 0.23 (5132 hom., cov: 34)
  • Exomes 𝑓: 0.30 (52005 hom.)
• Consequence: TES NM_015641.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.967

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TES	NM_015641.4	c.-87C>T		5_prime_UTR_variant	1/7	ENST00000358204.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TES	ENST00000358204.9	c.-87C>T		5_prime_UTR_variant	1/7	1	NM_015641.4	P1
	ENST00000624389.1	n.891G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35567 AN: 151864 Hom.: 5131 Cov.: 34

Gnomad AFR AF: 0.0603

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.240

GnomAD4 exome AF: 0.302 AC: 333455 AN: 1105436 Hom.: 52005 Cov.: 19 AF XY: 0.302 AC XY: 159997 AN XY: 530400

Gnomad4 AFR exome AF: 0.0465

Gnomad4 AMR exome AF: 0.383

Gnomad4 ASJ exome AF: 0.252

Gnomad4 EAS exome AF: 0.292

Gnomad4 SAS exome AF: 0.253

Gnomad4 FIN exome AF: 0.253

Gnomad4 NFE exome AF: 0.313

Gnomad4 OTH exome AF: 0.287

GnomAD4 genome AF: 0.234 AC: 35582 AN: 151972 Hom.: 5132 Cov.: 34 AF XY: 0.234 AC XY: 17422 AN XY: 74296

Gnomad4 AFR AF: 0.0602

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.240

Alfa AF: 0.141 Hom.: 301

Bravo AF: 0.234

Asia WGS AF: 0.199 AC: 684 AN: 3420

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	5.7
Dann	Benign	0.90
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11549785; hg19: chr7-115850675; COSMIC: COSV64042472;