7-116222242-A-T

Variant names:

• chr7-116222242-A-T
• rs1004109
• NM_015641.4:c.27+11508A>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.27+11508A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 151,866 control chromosomes in the GnomAD database, including 8,915 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 (8915 hom., cov: 32)
• Consequence: TES NM_015641.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 10 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 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.27+11508A>T		intron	N/A	NP_056456.1	A4D0U5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TES	ENST00000358204.9	TSL:1 MANE Select	c.27+11508A>T		intron	N/A	ENSP00000350937.4	Q9UGI8-1
	TES	ENST00000496871.1	TSL:1	n.174+11508A>T		intron	N/A
	TES	ENST00000937597.1		c.27+11508A>T		intron	N/A	ENSP00000607656.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50647 AN: 151748 Hom.: 8882 Cov.: 32

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.334 AC: 50737 AN: 151866 Hom.: 8915 Cov.: 32 AF XY: 0.340 AC XY: 25230 AN XY: 74222

African (AFR) AF: 0.435 AC: 18006 AN: 41374

American (AMR) AF: 0.294 AC: 4487 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 931 AN: 3468

East Asian (EAS) AF: 0.573 AC: 2954 AN: 5158

South Asian (SAS) AF: 0.354 AC: 1710 AN: 4824

European-Finnish (FIN) AF: 0.333 AC: 3500 AN: 10524

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18216 AN: 67934

Other (OTH) AF: 0.302 AC: 637 AN: 2110

Alfa AF: 0.196 Hom.: 429

Bravo AF: 0.334

Asia WGS AF: 0.509 AC: 1763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
DANN	Benign	0.59
PhyloP100		1.1
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: rs1004109; hg19: chr7-115862296;