2-159150437-C-G

Variant names:

• chr2-159150437-C-G
• rs1340714935
• NM_033394.3:c.563C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033394.3(TANC1):​c.563C>G​(p.Thr188Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T188N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TANC1 NM_033394.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14011827).

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.563C>G	p.Thr188Ser	missense	Exon 7 of 27	NP_203752.2	Q9C0D5-1
	TANC1	NM_001350064.2		c.563C>G	p.Thr188Ser	missense	Exon 7 of 27	NP_001336993.1
	TANC1	NM_001350065.2		c.563C>G	p.Thr188Ser	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.563C>G	p.Thr188Ser	missense	Exon 7 of 27	ENSP00000263635.6	Q9C0D5-1
	TANC1	ENST00000851031.1		c.617C>G	p.Thr206Ser	missense	Exon 8 of 28	ENSP00000521100.1
	TANC1	ENST00000950898.1		c.617C>G	p.Thr206Ser	missense	Exon 7 of 27	ENSP00000620957.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.072	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		7.9
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.14
Sift	Benign	0.16	T
Sift4G	Benign	0.44	T
Polyphen		0.10	B
Vest4		0.40
MutPred		0.078		Loss of glycosylation at S187 (P = 0.08)
MVP		0.39
MPC		0.38
ClinPred		0.72	D
GERP RS		5.5
Varity_R		0.11
gMVP		0.36
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1340714935; hg19: chr2-160006948;