rs2241023

Positions:

• chr2-159224825-G-C
• chr2-159224825-G-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.769

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TANC1	NM_033394.3	c.3811+461G>C		intron_variant		ENST00000263635.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TANC1	ENST00000263635.8	c.3811+461G>C		intron_variant		5	NM_033394.3	P1
TANC1	ENST00000496406.1	n.433G>C		non_coding_transcript_exon_variant	1/2	1
TANC1	ENST00000470074.1	n.933+461G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0863 AC: 13129 AN: 152084 Hom.: 1197 Cov.: 32

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.: 36 Cov.: 0 AF XY: 0.0430 AC XY: 258 AN XY: 6004

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.0183

Gnomad4 ASJ exome AF: 0.0543

Gnomad4 EAS exome AF: 0.209

Gnomad4 SAS exome AF: 0.0630

Gnomad4 FIN exome AF: 0.0203

Gnomad4 NFE exome AF: 0.0133

Gnomad4 OTH exome AF: 0.0285

GnomAD4 genome AF: 0.0863 AC: 13138 AN: 152202 Hom.: 1198 Cov.: 32 AF XY: 0.0885 AC XY: 6581 AN XY: 74400

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.0364

Gnomad4 ASJ AF: 0.0375

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.0713

Gnomad4 FIN AF: 0.0642

Gnomad4 NFE AF: 0.0152

Gnomad4 OTH AF: 0.0686

Alfa AF: 0.0189 Hom.: 21

Bravo AF: 0.0903

Asia WGS AF: 0.166 AC: 578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.81
DANN	Benign	0.51

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: rs2241023; hg19: chr2-160081336;