chr7-116257042-T-C

Variant names:

• chr7-116257042-T-C
• rs2402057
• NM_015641.4:c.1078-252T>C

Variant summary

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

The NM_015641.4(TES):​c.1078-252T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,056 control chromosomes in the GnomAD database, including 8,442 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 0.33 (8442 hom., cov: 32)
• Consequence: TES NM_015641.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 6 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]

LOC124901730 (HGNC:):

ENSG00000237813 (HGNC:40129):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TES	NM_015641.4	c.1078-252T>C		intron_variant	Intron 6 of 6	ENST00000358204.9	NP_056456.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TES	ENST00000358204.9	c.1078-252T>C		intron_variant	Intron 6 of 6	1	NM_015641.4	ENSP00000350937.4

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49554 AN: 151938 Hom.: 8427 Cov.: 32

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.293

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.326 AC: 49615 AN: 152056 Hom.: 8442 Cov.: 32 AF XY: 0.333 AC XY: 24772 AN XY: 74326

African (AFR) AF: 0.401 AC: 16646 AN: 41474

American (AMR) AF: 0.322 AC: 4915 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 920 AN: 3470

East Asian (EAS) AF: 0.577 AC: 2979 AN: 5162

South Asian (SAS) AF: 0.354 AC: 1709 AN: 4824

European-Finnish (FIN) AF: 0.332 AC: 3509 AN: 10568

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 18016 AN: 67968

Other (OTH) AF: 0.298 AC: 627 AN: 2106

Alfa AF: 0.315 Hom.: 1353

Bravo AF: 0.328

Asia WGS AF: 0.510 AC: 1766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.074
DANN	Benign	0.25
PhyloP100		-1.6
Mutation Taster		=100/0	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: rs2402057; hg19: chr7-115897096;