17-63009566-C-T

Position:

• chr17-63009566-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001394998.1(TANC2):​c.7C>T​(p.Arg3Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,586 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TANC2 NM_001394998.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.99

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TANC2	NM_001394998.1	c.7C>T	p.Arg3Trp	missense_variant	2/28	ENST00000689528.1	NP_001381927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TANC2	ENST00000689528.1	c.7C>T	p.Arg3Trp	missense_variant	2/28		NM_001394998.1	ENSP00000510600.1
TANC2	ENST00000424789.6	c.7C>T	p.Arg3Trp	missense_variant	1/25	1		ENSP00000387593.2
TANC2	ENST00000389520.8	c.7C>T	p.Arg3Trp	missense_variant	1/26	5		ENSP00000374171.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460586 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726594

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2024

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.2	N;N
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		1.0	D;.
Vest4		0.61
MutPred		0.23		Loss of methylation at R3 (P = 0.0197);Loss of methylation at R3 (P = 0.0197);
MVP		0.50
MPC		0.30
ClinPred		0.86	D
GERP RS		5.6
Varity_R		0.25
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-61086927; COSMIC: COSV67343879; COSMIC: COSV67343879;