2-159219134-A-C

Variant names:

• chr2-159219134-A-C
• rs10490005
• NM_033394.3:c.3379-104A>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.3379-104A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 1,466,976 control chromosomes in the GnomAD database, including 3,614 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 (1210 hom., cov: 33)
  • Exomes 𝑓: 0.032 (2404 hom.)
• Consequence: TANC1 NM_033394.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.528
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 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.3379-104A>C		intron	N/A	NP_203752.2
	TANC1	NM_001350064.2		c.3358-104A>C		intron	N/A	NP_001336993.1
	TANC1	NM_001350065.2		c.3358-104A>C		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.3379-104A>C		intron	N/A	ENSP00000263635.6
	TANC1	ENST00000470074.1	TSL:5	n.171-104A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0867 AC: 13190 AN: 152200 Hom.: 1209 Cov.: 33

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: 0.0735

Gnomad FIN AF: 0.0643

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.0678

GnomAD4 exome AF: 0.0324 AC: 42548 AN: 1314658 Hom.: 2404 AF XY: 0.0329 AC XY: 21593 AN XY: 656930

African (AFR) AF: 0.217 AC: 6519 AN: 30048

American (AMR) AF: 0.0225 AC: 969 AN: 43002

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 960 AN: 24332

East Asian (EAS) AF: 0.241 AC: 9277 AN: 38504

South Asian (SAS) AF: 0.0656 AC: 5320 AN: 81068

European-Finnish (FIN) AF: 0.0538 AC: 2829 AN: 52572

Middle Eastern (MID) AF: 0.0314 AC: 138 AN: 4392

European-Non Finnish (NFE) AF: 0.0145 AC: 14283 AN: 985706

Other (OTH) AF: 0.0409 AC: 2253 AN: 55034

GnomAD4 genome AF: 0.0867 AC: 13200 AN: 152318 Hom.: 1210 Cov.: 33 AF XY: 0.0889 AC XY: 6621 AN XY: 74486

African (AFR) AF: 0.217 AC: 9025 AN: 41548

American (AMR) AF: 0.0364 AC: 558 AN: 15312

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

East Asian (EAS) AF: 0.228 AC: 1183 AN: 5188

South Asian (SAS) AF: 0.0727 AC: 351 AN: 4828

European-Finnish (FIN) AF: 0.0643 AC: 683 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0153 AC: 1039 AN: 68030

Other (OTH) AF: 0.0690 AC: 146 AN: 2116

Alfa AF: 0.0637 Hom.: 108

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	-0.90
CADD	Benign	3.5
DANN	Benign	0.52
PhyloP100		0.53
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: rs10490005; hg19: chr2-160075645; COSMIC: COSV55094433;