2-159219629-A-G

Variant names:

• chr2-159219629-A-G
• rs10490004
• NM_033394.3:c.3503-63A>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.3503-63A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0376 in 1,600,384 control chromosomes in the GnomAD database, including 3,821 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 0.087 (1207 hom., cov: 32)
  • Exomes 𝑓: 0.032 (2614 hom.)
• Consequence: TANC1 NM_033394.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 4 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033394.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANC1	NM_033394.3	MANE Select	c.3503-63A>G		intron	N/A	NP_203752.2
	TANC1	NM_001350064.2		c.3482-63A>G		intron	N/A	NP_001336993.1
	TANC1	NM_001350065.2		c.3482-63A>G		intron	N/A	NP_001336994.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANC1	ENST00000263635.8	TSL:5 MANE Select	c.3503-63A>G		intron	N/A	ENSP00000263635.6
	TANC1	ENST00000470074.1	TSL:5	n.562A>G		non_coding_transcript_exon	Exon 3 of 8

Frequencies

GnomAD3 genomes AF: 0.0866 AC: 13174 AN: 152068 Hom.: 1206 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0366

Gnomad ASJ AF: 0.0375

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.0731

Gnomad FIN AF: 0.0637

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.0681

GnomAD2 exomes AF: 0.0558 AC: 13886 AN: 248772 AF XY: 0.0529

Gnomad AFR exome AF: 0.227

Gnomad AMR exome AF: 0.0207

Gnomad ASJ exome AF: 0.0385

Gnomad EAS exome AF: 0.218

Gnomad FIN exome AF: 0.0565

Gnomad NFE exome AF: 0.0163

Gnomad OTH exome AF: 0.0366

GnomAD4 exome AF: 0.0324 AC: 46977 AN: 1448198 Hom.: 2614 Cov.: 30 AF XY: 0.0329 AC XY: 23716 AN XY: 721174

African (AFR) AF: 0.222 AC: 7358 AN: 33140

American (AMR) AF: 0.0223 AC: 995 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.0401 AC: 1045 AN: 26030

East Asian (EAS) AF: 0.242 AC: 9586 AN: 39630

South Asian (SAS) AF: 0.0664 AC: 5693 AN: 85686

European-Finnish (FIN) AF: 0.0538 AC: 2857 AN: 53134

Middle Eastern (MID) AF: 0.0331 AC: 190 AN: 5748

European-Non Finnish (NFE) AF: 0.0152 AC: 16724 AN: 1100222

Other (OTH) AF: 0.0422 AC: 2529 AN: 59986

GnomAD4 genome AF: 0.0866 AC: 13184 AN: 152186 Hom.: 1207 Cov.: 32 AF XY: 0.0889 AC XY: 6615 AN XY: 74410

African (AFR) AF: 0.217 AC: 9018 AN: 41498

American (AMR) AF: 0.0366 AC: 559 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0375 AC: 130 AN: 3470

East Asian (EAS) AF: 0.228 AC: 1184 AN: 5184

South Asian (SAS) AF: 0.0723 AC: 349 AN: 4824

European-Finnish (FIN) AF: 0.0637 AC: 675 AN: 10598

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0153 AC: 1038 AN: 68012

Other (OTH) AF: 0.0693 AC: 146 AN: 2108

Alfa AF: 0.0548 Hom.: 117

Bravo AF: 0.0905

Asia WGS AF: 0.166 AC: 576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.0080
DANN	Benign	0.18
PhyloP100		-2.1
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: rs10490004; hg19: chr2-160076140; COSMIC: COSV55088558; COSMIC: COSV55088558;