rs748774322

Variant names:

• chr2-159149172-C-T
• rs748774322
• NM_033394.3:c.395C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_033394.3(TANC1):​c.395C>T​(p.Ser132Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,609,672 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: TANC1 NM_033394.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.38
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.395C>T	p.Ser132Leu	missense	Exon 6 of 27	NP_203752.2	Q9C0D5-1
	TANC1	NM_001350064.2		c.395C>T	p.Ser132Leu	missense	Exon 6 of 27	NP_001336993.1
	TANC1	NM_001350065.2		c.395C>T	p.Ser132Leu	missense	Exon 7 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.395C>T	p.Ser132Leu	missense	Exon 6 of 27	ENSP00000263635.6	Q9C0D5-1
	TANC1	ENST00000851031.1		c.449C>T	p.Ser150Leu	missense	Exon 7 of 28	ENSP00000521100.1
	TANC1	ENST00000950898.1		c.449C>T	p.Ser150Leu	missense	Exon 6 of 27	ENSP00000620957.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152170 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: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000243 AC: 6 AN: 247296 AF XY: 0.0000224

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000303

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000889

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1457502 Hom.: 0 Cov.: 31 AF XY: 0.0000152 AC XY: 11 AN XY: 724386

African (AFR) AF: 0.00 AC: 0 AN: 33358

American (AMR) AF: 0.0000677 AC: 3 AN: 44336

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 25978

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39618

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000902 AC: 10 AN: 1109192

Other (OTH) AF: 0.0000332 AC: 2 AN: 60208

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74324

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15276

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000248 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.51	D
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.4
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.23
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.26		Gain of catalytic residue at S132 (P = 0.0053)
MVP		0.46
MPC		0.69
ClinPred		0.91	D
GERP RS		5.8
Varity_R		0.34
gMVP		0.49
Mutation Taster		=50/50

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

Other links and lift over

dbSNP: rs748774322; hg19: chr2-160005683;