chr2-159163390-C-T

Variant names:

• chr2-159163390-C-T
• rs55929944
• NM_033394.3:c.790C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033394.3(TANC1):​c.790C>T​(p.Arg264Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00617 in 1,614,158 control chromosomes in the GnomAD database, including 533 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (279 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (254 hom.)
• Consequence: TANC1 NM_033394.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.01
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019655824).
• BP6: Variant 2-159163390-C-T is Benign according to our data. Variant chr2-159163390-C-T is described in ClinVar as Benign. ClinVar VariationId is 775764.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANC1	NM_033394.3	MANE Select	c.790C>T	p.Arg264Cys	missense	Exon 8 of 27	NP_203752.2	Q9C0D5-1
	TANC1	NM_001350064.2		c.790C>T	p.Arg264Cys	missense	Exon 8 of 27	NP_001336993.1
	TANC1	NM_001350065.2		c.790C>T	p.Arg264Cys	missense	Exon 9 of 28	NP_001336994.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANC1	ENST00000263635.8	TSL:5 MANE Select	c.790C>T	p.Arg264Cys	missense	Exon 8 of 27	ENSP00000263635.6	Q9C0D5-1
	TANC1	ENST00000851031.1		c.844C>T	p.Arg282Cys	missense	Exon 9 of 28	ENSP00000521100.1
	TANC1	ENST00000950898.1		c.844C>T	p.Arg282Cys	missense	Exon 8 of 27	ENSP00000620957.1

Frequencies

GnomAD3 genomes AF: 0.0327 AC: 4977 AN: 152162 Hom.: 277 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.0250

GnomAD2 exomes AF: 0.00809 AC: 2017 AN: 249230 AF XY: 0.00612

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.00426

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000505

Gnomad OTH exome AF: 0.00281

GnomAD4 exome AF: 0.00341 AC: 4980 AN: 1461878 Hom.: 254 Cov.: 34 AF XY: 0.00296 AC XY: 2152 AN XY: 727242

African (AFR) AF: 0.119 AC: 3989 AN: 33476

American (AMR) AF: 0.00487 AC: 218 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000348 AC: 30 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00468 AC: 27 AN: 5766

European-Non Finnish (NFE) AF: 0.000246 AC: 273 AN: 1112004

Other (OTH) AF: 0.00733 AC: 443 AN: 60396

GnomAD4 genome AF: 0.0327 AC: 4985 AN: 152280 Hom.: 279 Cov.: 32 AF XY: 0.0308 AC XY: 2296 AN XY: 74458

African (AFR) AF: 0.114 AC: 4725 AN: 41554

American (AMR) AF: 0.0108 AC: 165 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68030

Other (OTH) AF: 0.0247 AC: 52 AN: 2106

Alfa AF: 0.0124 Hom.: 177

Bravo AF: 0.0368

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.111 AC: 436

ESP6500EA AF: 0.000241 AC: 2

ExAC AF: 0.00975 AC: 1179

Asia WGS AF: 0.00722 AC: 25 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000889

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M
PhyloP100		5.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.20
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.013	D
Polyphen		0.11	B
Vest4		0.60
MVP		0.50
MPC		0.78
ClinPred		0.027	T
GERP RS		6.0
Varity_R		0.14
gMVP		0.33
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: rs55929944; hg19: chr2-160019901;