12-117099266-G-A

Variant names:

• chr12-117099266-G-A
• rs1402687997
• NM_017899.4:c.17C>T

Variant summary

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

The NM_017899.4(TESC):​c.17C>T​(p.Ser6Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000988 in 1,315,298 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000099 (0 hom.)
• Consequence: TESC NM_017899.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.68

Genes affected

TESC (HGNC:26065): (tescalcin) Enables calcium ion binding activity. Involved in several processes, including cellular response to retinoic acid; positive regulation of macromolecule metabolic process; and positive regulation of myeloid cell differentiation. Located in several cellular components, including cytosol; lamellipodium; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TESC-AS1 (HGNC:51142): (TESC antisense RNA 1 (head to head))

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=0.33311033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TESC	NM_017899.4	c.17C>T	p.Ser6Phe	missense_variant	Exon 1 of 8	ENST00000335209.12	NP_060369.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TESC	ENST00000335209.12	c.17C>T	p.Ser6Phe	missense_variant	Exon 1 of 8	1	NM_017899.4	ENSP00000334785.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000988 AC: 13 AN: 1315298 Hom.: 0 Cov.: 30 AF XY: 0.00000772 AC XY: 5 AN XY: 647972

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: 0.0000124

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.000187 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 10, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.17C>T (p.S6F) alteration is located in exon 1 (coding exon 1) of the TESC gene. This alteration results from a C to T substitution at nucleotide position 17, causing the serine (S) at amino acid position 6 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	Benign	0.24
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.38	T;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.79	T;T
M_CAP	Pathogenic	0.97	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Pathogenic	3.3	M;M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-4.0	D;D
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.0030	B;.
Vest4		0.26
MutPred		0.37		Loss of phosphorylation at S6 (P = 0.0175);Loss of phosphorylation at S6 (P = 0.0175);
MVP		0.23
MPC		0.51
ClinPred		0.99	D
GERP RS		2.3
Varity_R		0.63
gMVP		0.64

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: rs1402687997; hg19: chr12-117537071;