Genetic Variant TANC1:c.3811+461G>C (chr2-159224825-G-C) – 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.3811+461G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0832 in 163,718 control chromosomes in the GnomAD database, including 1,234 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 0.086 ( 1198 hom., cov: 32)

Exomes 𝑓: 0.042 ( 36 hom. )

Consequence

TANC1
NM_033394.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.769

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:

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 (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 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.3811+461G>C	intron	N/A	NP_203752.2	Q9C0D5-1
TANC1	NM_001350064.2		c.3790+461G>C	intron	N/A	NP_001336993.1
TANC1	NM_001350065.2		c.3790+461G>C	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.3811+461G>C	intron	N/A	ENSP00000263635.6	Q9C0D5-1
TANC1	ENST00000496406.1	TSL:1	n.433G>C	non_coding_transcript_exon	Exon 1 of 2
TANC1	ENST00000851031.1		c.3865+461G>C	intron	N/A	ENSP00000521100.1

Frequencies

GnomAD3 genomes

AF:

0.0863

AC:

13129

AN:

152084

Hom.:

1197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.0365

Gnomad ASJ

AF:

0.0375

Gnomad EAS

AF:

0.228

Gnomad SAS

AF:

0.0720

Gnomad FIN

AF:

0.0642

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0152

Gnomad OTH

AF:

0.0674

GnomAD4 exome

AF:

0.0418

AC:

481

AN:

11516

Hom.:

Cov.:

AF XY:

0.0430

AC XY:

258

AN XY:

6004

show subpopulations

African (AFR)

AF:

0.171

AC:

AN:

572

American (AMR)

AF:

0.0183

AC:

AN:

2130

Ashkenazi Jewish (ASJ)

AF:

0.0543

AC:

AN:

184

East Asian (EAS)

AF:

0.209

AC:

173

AN:

828

South Asian (SAS)

AF:

0.0630

AC:

AN:

968

European-Finnish (FIN)

AF:

0.0203

AC:

AN:

148

Middle Eastern (MID)

AF:

0.0417

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0133

AC:

AN:

6170

Other (OTH)

AF:

0.0285

AC:

AN:

492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

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:

0.0863

AC:

13138

AN:

152202

Hom.:

1198

Cov.:

AF XY:

0.0885

AC XY:

6581

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.216

AC:

8984

AN:

41510

American (AMR)

AF:

0.0364

AC:

557

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0375

AC:

130

AN:

3470

East Asian (EAS)

AF:

0.228

AC:

1176

AN:

5162

South Asian (SAS)

AF:

0.0713

AC:

343

AN:

4814

European-Finnish (FIN)

AF:

0.0642

AC:

681

AN:

10612

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0152

AC:

1037

AN:

68016

Other (OTH)

AF:

0.0686

AC:

145

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

539

1078

1616

2155

2694

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:

0.0189

Hom.:

Bravo

AF:

0.0903

Asia WGS

AF:

0.166

AC:

578

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.81

(source)

DANN

Benign

0.51

PhyloP100

-0.77

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

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