rs2402057

Positions:

• chr7-116257042-T-C

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TES	NM_015641.4	c.1078-252T>C		intron_variant		ENST00000358204.9	NP_056456.1
LOC124901730	XR_007060484.1	n.263A>G		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TES	ENST00000358204.9	c.1078-252T>C		intron_variant		1	NM_015641.4	ENSP00000350937	P1
	ENST00000444244.1	n.66-1807A>G		intron_variant, non_coding_transcript_variant		3
	ENST00000446355.2	n.204-13106A>G		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.298

Alfa AF: 0.311 Hom.: 1279

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

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: rs2402057; hg19: chr7-115897096;