17-40478310-G-A

Position:

• chr17-40478310-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000254051.11(TNS4):​c.2003C>T​(p.Ser668Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TNS4 ENST00000254051.11 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.29

Genes affected

TNS4 (HGNC:24352): (tensin 4) Predicted to enable actin binding activity. Involved in protein localization. Located in focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

TNS4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.827

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNS4	NM_032865.6	c.2003C>T	p.Ser668Phe	missense_variant	12/13	ENST00000254051.11	NP_116254.4
TNS4	XM_047436949.1	c.2339C>T	p.Ser780Phe	missense_variant	12/13		XP_047292905.1
TNS4	XM_005257744.2	c.2000C>T	p.Ser667Phe	missense_variant	12/13		XP_005257801.1
TNS4	XM_017025236.2	c.1925C>T	p.Ser642Phe	missense_variant	11/12		XP_016880725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNS4	ENST00000254051.11	c.2003C>T	p.Ser668Phe	missense_variant	12/13	1	NM_032865.6	ENSP00000254051.6
TNS4	ENST00000394072.7	n.269C>T		non_coding_transcript_exon_variant	3/4	1
TNS4	ENST00000582747.1	c.92C>T	p.Ser31Phe	missense_variant	2/2	3		ENSP00000463456.1
TNS4	ENST00000497303.1	n.432C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Sep 07, 2022

The c.2003C>T (p.S668F) alteration is located in exon 12 (coding exon 11) of the TNS4 gene. This alteration results from a C to T substitution at nucleotide position 2003, causing the serine (S) at amino acid position 668 to be replaced by a phenylalanine (F). 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	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.46	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.70		Gain of helix (P = 0.062);
MVP		0.85
MPC		0.68
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.71
gMVP		0.66

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: chr17-38634562; COSMIC: COSV54184782; COSMIC: COSV54184782;