Genetic Variant NM_017899.4:c.350-9C>A (chr12-117046847-G-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_017899.4(TESC):c.350-9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000739 in 1,563,866 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00038 ( 1 hom. )

Consequence

TESC
NM_017899.4 intron

Scores

Splicing: ADA: 0.0004906

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0670

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 12-117046847-G-T is Benign according to our data. Variant chr12-117046847-G-T is described in ClinVar as Benign. ClinVar VariationId is 791322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

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	Effect	Exon Rank	Protein	UniProt
TESC	NM_017899.4	MANE Select	c.350-9C>A	intron	N/A	NP_060369.3	Q96BS2-1
TESC	NM_001168325.2		c.269-9C>A	intron	N/A	NP_001161797.1	Q96BS2-3
TESC	NR_031766.3		n.484-9C>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TESC	ENST00000335209.12	TSL:1 MANE Select	c.350-9C>A	intron	N/A	ENSP00000334785.7	Q96BS2-1
TESC	ENST00000940881.1		c.350-9C>A	intron	N/A	ENSP00000610940.1
TESC	ENST00000874651.1		c.350-9C>A	intron	N/A	ENSP00000544710.1

Frequencies

GnomAD3 genomes

AF:

0.00403

AC:

613

AN:

151992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.000976

AC:

167

AN:

171044

AF XY:

0.000773

show subpopulations

Gnomad AFR exome

AF:

0.0134

Gnomad AMR exome

AF:

0.00100

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:

0.000863

GnomAD4 exome

AF:

0.000375

AC:

530

AN:

1411754

Hom.:

Cov.:

AF XY:

0.000333

AC XY:

232

AN XY:

697370

show subpopulations

African (AFR)

AF:

0.0116

AC:

378

AN:

32550

American (AMR)

AF:

0.00111

AC:

AN:

37056

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25306

East Asian (EAS)

AF:

0.00

AC:

AN:

37338

South Asian (SAS)

AF:

0.0000498

AC:

AN:

80250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48880

Middle Eastern (MID)

AF:

0.00123

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

1086108

Other (OTH)

AF:

0.00143

AC:

AN:

58552

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

107

134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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

AF:

0.00412

AC:

626

AN:

152112

Hom.:

Cov.:

AF XY:

0.00393

AC XY:

292

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0135

AC:

562

AN:

41516

American (AMR)

AF:

0.00373

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5122

South Asian (SAS)

AF:

0.000208

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67968

Other (OTH)

AF:

0.00190

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

105

131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00214

Hom.:

Bravo

AF:

0.00452

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

0.067

PromoterAI

0.0018

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00049

dbscSNV1_RF

Benign

0.068

SpliceAI score (max)

0.020

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over