Genetic Variant NM_033394.3:c.208C>A (chr2-159097783-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_033394.3(TANC1):c.208C>A(p.Leu70Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000929 in 1,614,022 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 12 hom., cov: 32)

Exomes 𝑓: 0.00049 ( 5 hom. )

Consequence

TANC1
NM_033394.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.61

Publications

0 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007663846).

BP6

Variant 2-159097783-C-A is Benign according to our data. Variant chr2-159097783-C-A is described in ClinVar as Benign. ClinVar VariationId is 775763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00517 (787/152200) while in subpopulation AFR AF = 0.018 (749/41510). AF 95% confidence interval is 0.017. There are 12 homozygotes in GnomAd4. There are 359 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 12 gene

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	HGVSp	Effect	Exon Rank	Protein	UniProt
TANC1	NM_033394.3	MANE Select	c.208C>A	p.Leu70Met	missense	Exon 4 of 27	NP_203752.2	Q9C0D5-1
TANC1	NM_001350064.2		c.208C>A	p.Leu70Met	missense	Exon 4 of 27	NP_001336993.1
TANC1	NM_001350065.2		c.208C>A	p.Leu70Met	missense	Exon 5 of 28	NP_001336994.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TANC1	ENST00000263635.8	TSL:5 MANE Select	c.208C>A	p.Leu70Met	missense	Exon 4 of 27	ENSP00000263635.6	Q9C0D5-1
TANC1	ENST00000851031.1		c.262C>A	p.Leu88Met	missense	Exon 5 of 28	ENSP00000521100.1
TANC1	ENST00000950898.1		c.262C>A	p.Leu88Met	missense	Exon 4 of 27	ENSP00000620957.1

Frequencies

GnomAD3 genomes

AF:

0.00509

AC:

774

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0178

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00116

AC:

290

AN:

249458

AF XY:

0.000768

show subpopulations

Gnomad AFR exome

AF:

0.0162

Gnomad AMR exome

AF:

0.000927

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000488

AC:

713

AN:

1461822

Hom.:

Cov.:

AF XY:

0.000408

AC XY:

297

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.0161

AC:

539

AN:

33480

American (AMR)

AF:

0.000961

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53364

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000207

AC:

AN:

1111998

Other (OTH)

AF:

0.00166

AC:

100

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

110

146

183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.00517

AC:

787

AN:

152200

Hom.:

Cov.:

AF XY:

0.00482

AC XY:

359

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0180

AC:

749

AN:

41510

American (AMR)

AF:

0.00183

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68022

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

121

162

202

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:

0.00190

Hom.:

Bravo

AF:

0.00584

ESP6500AA

AF:

0.0159

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.00145

AC:

176

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.0077

MetaSVM

Uncertain

-0.078

MutationAssessor

Uncertain

2.5

PhyloP100

2.6

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.46

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.014

Polyphen

1.0

Vest4

0.41

MVP

0.73

MPC

0.72

ClinPred

0.036

GERP RS

5.3

Varity_R

0.50

gMVP

0.047

Mutation Taster

=84/16

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over