chr7-116210621-C-T

Variant names:

• chr7-116210621-C-T
• rs11549785
• NM_015641.4:c.-87C>T

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015641.4. 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.-87C>T		5_prime_UTR	Exon 1 of 7	NP_056456.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TES	ENST00000358204.9	TSL:1 MANE Select	c.-87C>T		5_prime_UTR	Exon 1 of 7	ENSP00000350937.4
	TES	ENST00000496871.1	TSL:1	n.61C>T		non_coding_transcript_exon	Exon 1 of 2
	TES	ENST00000937597.1		c.-87C>T		5_prime_UTR	Exon 1 of 7	ENSP00000607656.1

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

African (AFR) AF: 0.0465 AC: 1041 AN: 22372

American (AMR) AF: 0.383 AC: 3776 AN: 9852

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 3665 AN: 14564

East Asian (EAS) AF: 0.292 AC: 7462 AN: 25528

South Asian (SAS) AF: 0.253 AC: 7972 AN: 31524

European-Finnish (FIN) AF: 0.253 AC: 9659 AN: 38180

Middle Eastern (MID) AF: 0.280 AC: 1224 AN: 4368

European-Non Finnish (NFE) AF: 0.313 AC: 286178 AN: 915568

Other (OTH) AF: 0.287 AC: 12478 AN: 43480

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

African (AFR) AF: 0.0602 AC: 2498 AN: 41528

American (AMR) AF: 0.342 AC: 5219 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 877 AN: 3472

East Asian (EAS) AF: 0.283 AC: 1458 AN: 5160

South Asian (SAS) AF: 0.243 AC: 1173 AN: 4826

European-Finnish (FIN) AF: 0.256 AC: 2694 AN: 10526

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.306 AC: 20761 AN: 67890

Other (OTH) AF: 0.240 AC: 506 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.7
DANN	Benign	0.90
PhyloP100		-0.97
PromoterAI		-0.018	Neutral
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.2
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: rs11549785; hg19: chr7-115850675; COSMIC: COSV64042472;