17-63073993-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001394998.1(TANC2):c.118C>T(p.Arg40Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000499 in 1,583,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

TANC2
NM_001394998.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.45

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: Illumina, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen
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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026119113).

BP6

Variant 17-63073993-C-T is Benign according to our data. Variant chr17-63073993-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2377803.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000199 (30/151086) while in subpopulation AFR AF = 0.000681 (28/41144). AF 95% confidence interval is 0.000483. There are 0 homozygotes in GnomAd4. There are 14 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 30 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TANC2	NM_001394998.1 link	c.118C>T	p.Arg40Cys	missense_variant	Exon 3 of 28	ENST00000689528.1	NP_001381927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TANC2	ENST00000689528.1 link	c.118C>T	p.Arg40Cys	missense_variant	Exon 3 of 28		NM_001394998.1	ENSP00000510600.1		A0A8I5KXR5

Frequencies

GnomAD3 genomes

AF:

0.000199

AC:

AN:

150966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000683

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000660

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000197

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000825

AC:

AN:

205990

AF XY:

0.0000818

show subpopulations

Gnomad AFR exome

AF:

0.000966

Gnomad AMR exome

AF:

0.0000669

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1432580

Hom.:

Cov.:

AF XY:

0.0000324

AC XY:

AN XY:

709780

show subpopulations

African (AFR)

AF:

0.000946

AC:

AN:

32758

American (AMR)

AF:

0.0000488

AC:

AN:

40976

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25542

East Asian (EAS)

AF:

0.000104

AC:

AN:

38336

South Asian (SAS)

AF:

0.0000246

AC:

AN:

81404

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00000273

AC:

AN:

1097020

Other (OTH)

AF:

0.000118

AC:

AN:

59280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000199

AC:

AN:

151086

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

AN XY:

73860

show subpopulations

African (AFR)

AF:

0.000681

AC:

AN:

41144

American (AMR)

AF:

0.0000659

AC:

AN:

15174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.000197

AC:

AN:

5066

South Asian (SAS)

AF:

0.00

AC:

AN:

4738

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10544

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67684

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000183

Hom.:

Bravo

AF:

0.000261

ESP6500AA

AF:

0.00110

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.000116

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Aug 04, 2021

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.091

T;.;.

Eigen

Benign

-0.16

Eigen_PC

Benign

0.057

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.0072

MetaRNN

Benign

0.026

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;.

PhyloP100

3.4

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.3

N;N;.

REVEL

Benign

0.21

Sift

Benign

0.079

T;T;.

Sift4G

Benign

0.13

T;T;D

Polyphen

0.0

B;.;.

Vest4

0.60

MVP

0.36

MPC

0.39

ClinPred

0.064

GERP RS

5.0

PromoterAI

-0.022

Neutral

(source)

Varity_R

0.080

gMVP

0.15

Mutation Taster

=77/23

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

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17-63073993-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over