7-116257430-C-T

Position:

• chr7-116257430-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015641.4(TES):​c.1214C>T​(p.Pro405Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TES NM_015641.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.09

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40026587).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TES	NM_015641.4	c.1214C>T	p.Pro405Leu	missense_variant	7/7	ENST00000358204.9	NP_056456.1
TES	NM_152829.3	c.1187C>T	p.Pro396Leu	missense_variant	7/7		NP_690042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TES	ENST00000358204.9	c.1214C>T	p.Pro405Leu	missense_variant	7/7	1	NM_015641.4	ENSP00000350937	P1
	ENST00000444244.1	n.66-2195G>A		intron_variant, non_coding_transcript_variant		3
	ENST00000446355.2	n.204-13494G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Apr 20, 2024

The c.1214C>T (p.P405L) alteration is located in exon 7 (coding exon 7) of the TES gene. This alteration results from a C to T substitution at nucleotide position 1214, causing the proline (P) at amino acid position 405 to be replaced by a leucine (L). 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	0.29
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.74	D;.
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.40	T;T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Uncertain	0.39
Sift	Benign	0.18	T;T
Sift4G	Benign	0.81	T;T
Polyphen		0.081	B;.
Vest4		0.46
MutPred		0.47		Loss of ubiquitination at K402 (P = 0.0896);.;
MVP		0.92
MPC		0.15
ClinPred		0.97	D
GERP RS		5.6
Varity_R		0.40
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-115897484;