Genetic Variant NM_017899.4:c.17C>T (chr12-117099266-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S6P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000099 ( 0 hom. )

Consequence

TESC
NM_017899.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.68

Publications

0 publications found

Variant links:

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 links:

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

TESC-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33311033).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017899.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TESC	NM_017899.4	MANE Select	c.17C>T	p.Ser6Phe	missense	Exon 1 of 8	NP_060369.3	Q96BS2-1
TESC	NM_001168325.2		c.17C>T	p.Ser6Phe	missense	Exon 1 of 7	NP_001161797.1	Q96BS2-3
TESC	NR_031766.3		n.151C>T		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TESC	ENST00000335209.12	TSL:1 MANE Select	c.17C>T	p.Ser6Phe	missense	Exon 1 of 8	ENSP00000334785.7	Q96BS2-1
TESC	ENST00000940881.1		c.17C>T	p.Ser6Phe	missense	Exon 1 of 8	ENSP00000610940.1
TESC	ENST00000874651.1		c.17C>T	p.Ser6Phe	missense	Exon 1 of 7	ENSP00000544710.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

68738

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000988

AC:

AN:

1315298

Hom.:

Cov.:

AF XY:

0.00000772

AC XY:

AN XY:

647972

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26306

American (AMR)

AF:

0.00

AC:

AN:

25268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22744

East Asian (EAS)

AF:

0.00

AC:

AN:

28266

South Asian (SAS)

AF:

0.00

AC:

AN:

72410

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4072

European-Non Finnish (NFE)

AF:

0.0000124

AC:

AN:

1049204

Other (OTH)

AF:

0.00

AC:

AN:

54502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.000187

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.38

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.79

M_CAP

Pathogenic

0.97

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.67

MutationAssessor

Pathogenic

3.3

PhyloP100

2.7

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.13

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

0.0030

Vest4

0.26

MutPred

0.37

Loss of phosphorylation at S6 (P = 0.0175)

MVP

0.23

MPC

0.51

ClinPred

0.99

GERP RS

2.3

PromoterAI

0.016

Neutral

(source)

Varity_R

0.63

gMVP

0.64

Mutation Taster

=70/30

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over