NM_033394.3:c.572C>T

Variant names:

• chr2-159150446-C-T
• rs1190030881
• NM_033394.3:c.572C>T

Variant summary

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

The NM_033394.3(TANC1):​c.572C>T​(p.Pro191Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P191S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TANC1 NM_033394.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91
• Publications: 2 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.572C>T	p.Pro191Leu	missense	Exon 7 of 27	NP_203752.2	Q9C0D5-1
	TANC1	NM_001350064.2		c.572C>T	p.Pro191Leu	missense	Exon 7 of 27	NP_001336993.1
	TANC1	NM_001350065.2		c.572C>T	p.Pro191Leu	missense	Exon 8 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.572C>T	p.Pro191Leu	missense	Exon 7 of 27	ENSP00000263635.6	Q9C0D5-1
	TANC1	ENST00000851031.1		c.626C>T	p.Pro209Leu	missense	Exon 8 of 28	ENSP00000521100.1
	TANC1	ENST00000950898.1		c.626C>T	p.Pro209Leu	missense	Exon 7 of 27	ENSP00000620957.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249512 AF XY: 0.00

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: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	2.0	M
PhyloP100		7.9
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.021	D
Polyphen		0.69	P
Vest4		0.67
MutPred		0.11		Loss of loop (P = 0.0112)
MVP		0.58
MPC		0.57
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.42
gMVP		0.69
Mutation Taster		=37/63	disease causing

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: rs1190030881; hg19: chr2-160006957; COSMIC: COSV99712910;