rs6432512

Variant names:

• chr2-159043401-C-T
• rs6432512
• NM_033394.3:c.-15-22495C>T

Variant summary

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

The NM_001350065.2(TANC1):​c.-59C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 151,950 control chromosomes in the GnomAD database, including 2,031 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 0.12 (2031 hom., cov: 31)
• Consequence: TANC1 NM_001350065.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62
• Publications: 7 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350065.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANC1	NM_033394.3	MANE Select	c.-15-22495C>T		intron	N/A	NP_203752.2	Q9C0D5-1
	TANC1	NM_001350065.2		c.-59C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 28	NP_001336994.1
	TANC1	NM_001350065.2		c.-59C>T		5_prime_UTR	Exon 3 of 28	NP_001336994.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANC1	ENST00000263635.8	TSL:5 MANE Select	c.-15-22495C>T		intron	N/A	ENSP00000263635.6	Q9C0D5-1
	TANC1	ENST00000950894.1		c.-59C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 28	ENSP00000620953.1
	TANC1	ENST00000950890.1		c.-59C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 26	ENSP00000620949.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18432 AN: 151832 Hom.: 2029 Cov.: 31

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.0496

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.0336

Gnomad FIN AF: 0.0718

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0277

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.121 AC: 18459 AN: 151950 Hom.: 2031 Cov.: 31 AF XY: 0.125 AC XY: 9267 AN XY: 74296

African (AFR) AF: 0.285 AC: 11801 AN: 41380

American (AMR) AF: 0.161 AC: 2453 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0496 AC: 172 AN: 3466

East Asian (EAS) AF: 0.162 AC: 838 AN: 5168

South Asian (SAS) AF: 0.0323 AC: 155 AN: 4794

European-Finnish (FIN) AF: 0.0718 AC: 758 AN: 10564

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0277 AC: 1885 AN: 67994

Other (OTH) AF: 0.108 AC: 227 AN: 2110

Alfa AF: 0.0589 Hom.: 948

Bravo AF: 0.137

Asia WGS AF: 0.122 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.074
DANN	Benign	0.37
PhyloP100		-2.6
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6432512;

hg19: chr2-159899913;