Genetic Variant NM_033394.3:c.3503-63A>G (chr2-159219629-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TANC1	NM_033394.3 link	c.3503-63A>G		intron_variant	Intron 21 of 26	ENST00000263635.8	NP_203752.2	Q9C0D5-1B9EK39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TANC1	ENST00000263635.8 link	c.3503-63A>G		intron_variant	Intron 21 of 26	5	NM_033394.3	ENSP00000263635.6		Q9C0D5-1
TANC1	ENST00000470074.1 link	n.562A>G		non_coding_transcript_exon_variant	Exon 3 of 8	5

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

GnomAD3 exomes

AF:

0.0558

AC:

13886

AN:

248772

Hom.:

1012

AF XY:

0.0529

AC XY:

7138

AN XY:

135046

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 SAS exome

AF:

0.0682

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

Gnomad4 AFR exome

AF:

0.222

Gnomad4 AMR exome

AF:

0.0223

Gnomad4 ASJ exome

AF:

0.0401

Gnomad4 EAS exome

AF:

0.242

Gnomad4 SAS exome

AF:

0.0664

Gnomad4 FIN exome

AF:

0.0538

Gnomad4 NFE exome

AF:

0.0152

Gnomad4 OTH exome

AF:

0.0422

GnomAD4 genome

AF:

0.0866

AC:

13184

AN:

152186

Hom.:

1207

Cov.:

AF XY:

0.0889

AC XY:

6615

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.217

Gnomad4 AMR

AF:

0.0366

Gnomad4 ASJ

AF:

0.0375

Gnomad4 EAS

AF:

0.228

Gnomad4 SAS

AF:

0.0723

Gnomad4 FIN

AF:

0.0637

Gnomad4 NFE

AF:

0.0153

Gnomad4 OTH

AF:

0.0693

Alfa

AF:

0.0506

Hom.:

Bravo

AF:

0.0905

Asia WGS

AF:

0.166

AC:

576

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.0080

DANN

Benign

0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over