17-63073989-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001394998.1(TANC2):c.114C>A(p.Asp38Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000234 in 1,583,004 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D38D) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 1 hom. )

Consequence

TANC2
NM_001394998.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.32

Publications

1 publications found

Variant links:

Genes affected

TANC2 (HGNC:30212): (tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2) Predicted to be involved in dense core granule cytoskeletal transport; regulation of dendritic spine development; and regulation of dendritic spine morphogenesis. Predicted to act upstream of or within in utero embryonic development. Located in dendritic spine. [provided by Alliance of Genome Resources, Apr 2022]

TANC2 Gene-Disease associations (from GenCC):

intellectual developmental disorder with autistic features and language delay, with or without seizures
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: ClinGen, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TANC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.04099247).

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.0000251 (36/1434402) while in subpopulation SAS AF = 0.000405 (33/81494). AF 95% confidence interval is 0.000296. There are 1 homozygotes in GnomAdExome4. There are 28 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High AC in GnomAdExome4 at 36 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394998.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TANC2	NM_001394998.1	MANE Select	c.114C>A	p.Asp38Glu	missense	Exon 3 of 28	NP_001381927.1	A0A8I5KXR5
TANC2	NM_001411076.1		c.114C>A	p.Asp38Glu	missense	Exon 3 of 27	NP_001398005.1	Q9HCD6-2
TANC2	NM_025185.4		c.114C>A	p.Asp38Glu	missense	Exon 3 of 26	NP_079461.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TANC2	ENST00000689528.1	MANE Select	c.114C>A	p.Asp38Glu	missense	Exon 3 of 28	ENSP00000510600.1	A0A8I5KXR5
TANC2	ENST00000424789.6	TSL:1	c.114C>A	p.Asp38Glu	missense	Exon 2 of 25	ENSP00000387593.2	Q9HCD6-1
TANC2	ENST00000389520.8	TSL:5	c.114C>A	p.Asp38Glu	missense	Exon 2 of 26	ENSP00000374171.4	Q9HCD6-2

Frequencies

GnomAD3 genomes

AF:

0.00000673

AC:

AN:

148602

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000216

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000617

AC:

AN:

210850

AF XY:

0.0000975

show subpopulations

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:

0.0000251

AC:

AN:

1434402

Hom.:

Cov.:

AF XY:

0.0000394

AC XY:

AN XY:

710866

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32836

American (AMR)

AF:

0.00

AC:

AN:

41320

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25582

East Asian (EAS)

AF:

0.00

AC:

AN:

38472

South Asian (SAS)

AF:

0.000405

AC:

AN:

81494

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51680

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1097934

Other (OTH)

AF:

0.0000337

AC:

AN:

59348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

AF:

0.00000673

AC:

AN:

148602

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72584

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40258

American (AMR)

AF:

0.00

AC:

AN:

14944

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3428

East Asian (EAS)

AF:

0.00

AC:

AN:

4974

South Asian (SAS)

AF:

0.000216

AC:

AN:

4634

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10438

Middle Eastern (MID)

AF:

0.00

AC:

AN:

298

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66714

Other (OTH)

AF:

0.00

AC:

AN:

2034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000416

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.040

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.77

M_CAP

Benign

0.0027

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

PhyloP100

1.3

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.21

REVEL

Benign

0.16

Sift

Benign

0.090

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.45

MutPred

0.12

Gain of sheet (P = 0.0507)

MVP

0.32

MPC

0.27

ClinPred

0.046

GERP RS

2.9

PromoterAI

-0.0068

Neutral

(source)

Varity_R

0.063

gMVP

0.20

Mutation Taster

=88/12

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