2-159097908-C-T

Position:

• chr2-159097908-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033394.3(TANC1):​c.259+74C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,242,178 control chromosomes in the GnomAD database, including 32,588 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 0.21 (3499 hom., cov: 32)
  • Exomes 𝑓: 0.22 (29089 hom.)
• Consequence: TANC1 NM_033394.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TANC1	NM_033394.3	c.259+74C>T		intron_variant		ENST00000263635.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TANC1	ENST00000263635.8	c.259+74C>T		intron_variant		5	NM_033394.3	P1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31799 AN: 151832 Hom.: 3490 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.198

GnomAD4 exome AF: 0.223 AC: 243114 AN: 1090230 Hom.: 29089 AF XY: 0.226 AC XY: 124073 AN XY: 547886

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.275

Gnomad4 SAS exome AF: 0.349

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.219

GnomAD4 genome AF: 0.210 AC: 31838 AN: 151948 Hom.: 3499 Cov.: 32 AF XY: 0.210 AC XY: 15563 AN XY: 74252

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.198

Alfa AF: 0.214 Hom.: 640

Bravo AF: 0.208

Asia WGS AF: 0.315 AC: 1096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.43
DANN	Benign	0.57

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

Other links and lift over

dbSNP: rs13414916; hg19: chr2-159954420; COSMIC: COSV55084681;