rs264631

Variant names:

• chr2-159094353-C-G
• rs264631
• NM_033394.3:c.62-3284C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033394.3(TANC1):​c.62-3284C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,178 control chromosomes in the GnomAD database, including 2,806 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 0.14 (2806 hom., cov: 32)
• Consequence: TANC1 NM_033394.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402
• Publications: 9 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TANC1	NM_033394.3	c.62-3284C>G		intron_variant	Intron 3 of 26	ENST00000263635.8	NP_203752.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TANC1	ENST00000263635.8	c.62-3284C>G		intron_variant	Intron 3 of 26	5	NM_033394.3	ENSP00000263635.6

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21355 AN: 152060 Hom.: 2797 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0481

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0732

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0286

Gnomad OTH AF: 0.127

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.141 AC: 21400 AN: 152178 Hom.: 2806 Cov.: 32 AF XY: 0.145 AC XY: 10802 AN XY: 74392

African (AFR) AF: 0.342 AC: 14197 AN: 41490

American (AMR) AF: 0.168 AC: 2571 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0481 AC: 167 AN: 3470

East Asian (EAS) AF: 0.148 AC: 767 AN: 5166

South Asian (SAS) AF: 0.112 AC: 537 AN: 4808

European-Finnish (FIN) AF: 0.0732 AC: 776 AN: 10608

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0286 AC: 1946 AN: 68018

Other (OTH) AF: 0.126 AC: 267 AN: 2114

Alfa AF: 0.0934 Hom.: 231

Bravo AF: 0.156

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.63
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs264631; hg19: chr2-159950865;