rs781235539

Variant names:

• chr17-63073989-C-A
• rs781235539
• NM_001394998.1:c.114C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-63073989-C-A
• chr17-63073989-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001394998.1(TANC2):​c.114C>A​(p.Asp38Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000234 in 1,583,004 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D38D) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000025 (1 hom.)
• Consequence: TANC2 NM_001394998.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 1 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.04099247).
• BS1: Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.0000251 (36/1434402) while in subpopulation SAS AF = 0.000405 (33/81494). AF 95% confidence interval is 0.000296. There are 1 homozygotes in GnomAdExome4. There are 28 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAdExome4 at 36 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TANC2	NM_001394998.1	c.114C>A	p.Asp38Glu	missense_variant	Exon 3 of 28	ENST00000689528.1	NP_001381927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TANC2	ENST00000689528.1	c.114C>A	p.Asp38Glu	missense_variant	Exon 3 of 28		NM_001394998.1	ENSP00000510600.1

Frequencies

GnomAD3 genomes AF: 0.00000673 AC: 1 AN: 148602 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000216

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000617 AC: 13 AN: 210850 AF XY: 0.0000975

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000251 AC: 36 AN: 1434402 Hom.: 1 Cov.: 30 AF XY: 0.0000394 AC XY: 28 AN XY: 710866

African (AFR) AF: 0.00 AC: 0 AN: 32836

American (AMR) AF: 0.00 AC: 0 AN: 41320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25582

East Asian (EAS) AF: 0.00 AC: 0 AN: 38472

South Asian (SAS) AF: 0.000405 AC: 33 AN: 81494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51680

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097934

Other (OTH) AF: 0.0000337 AC: 2 AN: 59348

GnomAD4 genome AF: 0.00000673 AC: 1 AN: 148602 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 72584

African (AFR) AF: 0.00 AC: 0 AN: 40258

American (AMR) AF: 0.00 AC: 0 AN: 14944

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3428

East Asian (EAS) AF: 0.00 AC: 0 AN: 4974

South Asian (SAS) AF: 0.000216 AC: 1 AN: 4634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66714

Other (OTH) AF: 0.00 AC: 0 AN: 2034

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000416 AC: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.040	T;.;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.041	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	N;N;.
PhyloP100		1.3
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	0.21	N;N;.
REVEL	Benign	0.16
Sift	Benign	0.090	T;T;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.45
MutPred		0.12		Gain of sheet (P = 0.0507);Gain of sheet (P = 0.0507);.;
MVP		0.32
MPC		0.27
ClinPred		0.046	T
GERP RS		2.9
PromoterAI		-0.0068	Neutral
Varity_R		0.063
gMVP		0.20
Mutation Taster		=88/12	polymorphism

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: rs781235539; hg19: chr17-61151350;