NM_001394998.1:c.1575+4358A>G

Variant names:

• chr17-63323448-A-G
• rs2447447
• NM_001394998.1:c.1575+4358A>G

Variant summary

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

The NM_001394998.1(TANC2):​c.1575+4358A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 152,054 control chromosomes in the GnomAD database, including 29,980 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 0.60 (29980 hom., cov: 32)
• Consequence: TANC2 NM_001394998.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471
• Publications: 7 publications found

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]

TANC2 Gene-Disease associations (from GenCC):

• intellectual developmental disorder with autistic features and language delay, with or without seizures

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Illumina, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000233635 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TANC2	NM_001394998.1	c.1575+4358A>G		intron_variant	Intron 11 of 27	ENST00000689528.1	NP_001381927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TANC2	ENST00000689528.1	c.1575+4358A>G		intron_variant	Intron 11 of 27		NM_001394998.1	ENSP00000510600.1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91154 AN: 151936 Hom.: 29918 Cov.: 32

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.600 AC: 91273 AN: 152054 Hom.: 29980 Cov.: 32 AF XY: 0.595 AC XY: 44196 AN XY: 74302

African (AFR) AF: 0.871 AC: 36160 AN: 41502

American (AMR) AF: 0.478 AC: 7297 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1661 AN: 3466

East Asian (EAS) AF: 0.165 AC: 854 AN: 5168

South Asian (SAS) AF: 0.493 AC: 2372 AN: 4814

European-Finnish (FIN) AF: 0.568 AC: 6004 AN: 10564

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35096 AN: 67962

Other (OTH) AF: 0.541 AC: 1141 AN: 2110

Alfa AF: 0.531 Hom.: 10745

Bravo AF: 0.601

Asia WGS AF: 0.413 AC: 1439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.62
PhyloP100		-0.47
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: rs2447447; hg19: chr17-61400809;