7-116249225-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015641.4(TES):c.319A>G(p.Asn107Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: TES NM_015641.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.08

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24370953).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TES	NM_015641.4	c.319A>G	p.Asn107Asp	missense_variant	3/7	ENST00000358204.9
LOC124901730	XR_007060484.1	n.2188-5289T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TES	ENST00000358204.9	c.319A>G	p.Asn107Asp	missense_variant	3/7	1	NM_015641.4	P1
	ENST00000444244.1	n.184-5289T>C		intron_variant, non_coding_transcript_variant		3
	ENST00000446355.2	n.204-5289T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461778 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727188

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.319A>G (p.N107D) alteration is located in exon 3 (coding exon 3) of the TES gene. This alteration results from a A to G substitution at nucleotide position 319, causing the asparagine (N) at amino acid position 107 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	19
Dann	Benign	0.81
DEOGEN2	Benign	0.097	T;T;.
Eigen	Benign	-0.21
Eigen_PC	Benign	0.041
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.69	T;T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.090	N;.;.
MutationTaster	Benign	0.85	D;D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.17	N;N;N
REVEL	Uncertain	0.31
Sift	Benign	0.77	T;T;T
Sift4G	Benign	0.89	T;T;T
Polyphen		0.0020	B;.;.
Vest4		0.34
MutPred		0.63		Gain of catalytic residue at N107 (P = 0.0664);.;.;
MVP		0.81
MPC		0.080
ClinPred		0.83	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.31

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: rs1357244890; hg19: chr7-115889279;