rs10497203

Variant names:

• chr2-158994911-A-C
• rs10497203
• NM_033394.3:c.-125-6169A>C

Variant summary

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

The NM_033394.3(TANC1):​c.-125-6169A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0719 in 152,298 control chromosomes in the GnomAD database, including 608 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 0.072 (608 hom., cov: 33)
• Consequence: TANC1 NM_033394.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TANC1	NM_033394.3	c.-125-6169A>C		intron_variant	Intron 1 of 26	ENST00000263635.8	NP_203752.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TANC1	ENST00000263635.8	c.-125-6169A>C		intron_variant	Intron 1 of 26	5	NM_033394.3	ENSP00000263635.6

Frequencies

GnomAD3 genomes AF: 0.0719 AC: 10937 AN: 152180 Hom.: 606 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0478

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.0719

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0266

Gnomad OTH AF: 0.0674

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

GnomAD4 genome AF: 0.0719 AC: 10952 AN: 152298 Hom.: 608 Cov.: 33 AF XY: 0.0763 AC XY: 5683 AN XY: 74472

African (AFR) AF: 0.117 AC: 4870 AN: 41562

American (AMR) AF: 0.142 AC: 2165 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0478 AC: 166 AN: 3472

East Asian (EAS) AF: 0.157 AC: 814 AN: 5178

South Asian (SAS) AF: 0.0251 AC: 121 AN: 4824

European-Finnish (FIN) AF: 0.0719 AC: 764 AN: 10622

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0266 AC: 1807 AN: 68028

Other (OTH) AF: 0.0672 AC: 142 AN: 2114

Alfa AF: 0.0438 Hom.: 358

Bravo AF: 0.0804

Asia WGS AF: 0.104 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.1
DANN	Benign	0.68
PhyloP100		0.0090
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10497203; hg19: chr2-159851423;