rs10512498

Positions:

• chr17-63076018-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001394998.1(TANC2):​c.139+2004C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 152,114 control chromosomes in the GnomAD database, including 98 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 0.034 (98 hom., cov: 32)
• Consequence: TANC2 NM_001394998.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310

Genes affected

TANC2 (HGNC:30212): (tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2) Predicted to be involved in dense core granule cytoskeletal transport; regulation of dendritic spine development; and regulation of dendritic spine morphogenesis. Predicted to act upstream of or within in utero embryonic development. Located in dendritic spine. [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).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0336 (5108/152114) while in subpopulation NFE AF= 0.0442 (3003/67972). AF 95% confidence interval is 0.0429. There are 98 homozygotes in gnomad4. There are 2425 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 5108 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TANC2	NM_001394998.1	c.139+2004C>G		intron_variant		ENST00000689528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TANC2	ENST00000689528.1	c.139+2004C>G		intron_variant			NM_001394998.1	P3

Frequencies

GnomAD3 genomes AF: 0.0336 AC: 5108 AN: 151996 Hom.: 97 Cov.: 32

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0405

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.0208

Gnomad FIN AF: 0.0313

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0442

Gnomad OTH AF: 0.0411

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

GnomAD4 genome AF: 0.0336 AC: 5108 AN: 152114 Hom.: 98 Cov.: 32 AF XY: 0.0326 AC XY: 2425 AN XY: 74356

Gnomad4 AFR AF: 0.0159

Gnomad4 AMR AF: 0.0405

Gnomad4 ASJ AF: 0.0513

Gnomad4 EAS AF: 0.0112

Gnomad4 SAS AF: 0.0210

Gnomad4 FIN AF: 0.0313

Gnomad4 NFE AF: 0.0442

Gnomad4 OTH AF: 0.0417

Alfa AF: 0.0344 Hom.: 10

Bravo AF: 0.0335

Asia WGS AF: 0.0350 AC: 121 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	1.9
DANN	Benign	0.66

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: rs10512498; hg19: chr17-61153379;