Genetic Variant TANC1:c.3503-63A>G (chr2-159219629-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033394.3(TANC1):c.3503-63A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0376 in 1,600,384 control chromosomes in the GnomAD database, including 3,821 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.087 ( 1207 hom., cov: 32)

Exomes 𝑓: 0.032 ( 2614 hom. )

Consequence

TANC1
NM_033394.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.09

Publications

4 publications found

Variant links:

Genes affected

TANC1 (HGNC:29364): (tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 1) Predicted to be involved in regulation of postsynapse organization. Predicted to act upstream of or within dendritic spine maintenance; myoblast fusion; and visual learning. Predicted to be located in several cellular components, including axon terminus; neuronal cell body; and postsynaptic density. Predicted to be active in glutamatergic synapse and postsynaptic density, intracellular component. [provided by Alliance of Genome Resources, Apr 2022]

TANC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033394.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TANC1	NM_033394.3	MANE Select	c.3503-63A>G	intron	N/A	NP_203752.2	Q9C0D5-1
TANC1	NM_001350064.2		c.3482-63A>G	intron	N/A	NP_001336993.1
TANC1	NM_001350065.2		c.3482-63A>G	intron	N/A	NP_001336994.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TANC1	ENST00000263635.8	TSL:5 MANE Select	c.3503-63A>G	intron	N/A	ENSP00000263635.6	Q9C0D5-1
TANC1	ENST00000851031.1		c.3557-63A>G	intron	N/A	ENSP00000521100.1
TANC1	ENST00000950898.1		c.3557-63A>G	intron	N/A	ENSP00000620957.1

Frequencies

GnomAD3 genomes

AF:

0.0866

AC:

13174

AN:

152068

Hom.:

1206

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.0366

Gnomad ASJ

AF:

0.0375

Gnomad EAS

AF:

0.229

Gnomad SAS

AF:

0.0731

Gnomad FIN

AF:

0.0637

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0153

Gnomad OTH

AF:

0.0681

GnomAD2 exomes

AF:

0.0558

AC:

13886

AN:

248772

AF XY:

0.0529

show subpopulations

Gnomad AFR exome

AF:

0.227

Gnomad AMR exome

AF:

0.0207

Gnomad ASJ exome

AF:

0.0385

Gnomad EAS exome

AF:

0.218

Gnomad FIN exome

AF:

0.0565

Gnomad NFE exome

AF:

0.0163

Gnomad OTH exome

AF:

0.0366

GnomAD4 exome

AF:

0.0324

AC:

46977

AN:

1448198

Hom.:

2614

Cov.:

AF XY:

0.0329

AC XY:

23716

AN XY:

721174

show subpopulations

African (AFR)

AF:

0.222

AC:

7358

AN:

33140

American (AMR)

AF:

0.0223

AC:

995

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.0401

AC:

1045

AN:

26030

East Asian (EAS)

AF:

0.242

AC:

9586

AN:

39630

South Asian (SAS)

AF:

0.0664

AC:

5693

AN:

85686

European-Finnish (FIN)

AF:

0.0538

AC:

2857

AN:

53134

Middle Eastern (MID)

AF:

0.0331

AC:

190

AN:

5748

European-Non Finnish (NFE)

AF:

0.0152

AC:

16724

AN:

1100222

Other (OTH)

AF:

0.0422

AC:

2529

AN:

59986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

2131

4262

6392

8523

10654

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

910

1820

2730

3640

4550

<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:

0.0866

AC:

13184

AN:

152186

Hom.:

1207

Cov.:

AF XY:

0.0889

AC XY:

6615

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.217

AC:

9018

AN:

41498

American (AMR)

AF:

0.0366

AC:

559

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0375

AC:

130

AN:

3470

East Asian (EAS)

AF:

0.228

AC:

1184

AN:

5184

South Asian (SAS)

AF:

0.0723

AC:

349

AN:

4824

European-Finnish (FIN)

AF:

0.0637

AC:

675

AN:

10598

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0153

AC:

1038

AN:

68012

Other (OTH)

AF:

0.0693

AC:

146

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

535

1070

1605

2140

2675

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<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:

0.0548

Hom.:

117

Bravo

AF:

0.0905

Asia WGS

AF:

0.166

AC:

576

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.0080

(source)

DANN

Benign

0.18

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(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

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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