NM_001128596.3:c.904C>A

Variant names:

• chr14-91792510-G-T
• NM_001128596.3:c.904C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001128596.3(TC2N):​c.904C>A​(p.Leu302Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,444,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TC2N NM_001128596.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.86
• Publications: 0 publications found

Genes affected

TC2N (HGNC:19859): (tandem C2 domains, nuclear) Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3101207).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128596.3. 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
	TC2N	NM_001128596.3	MANE Select	c.904C>A	p.Leu302Ile	missense	Exon 9 of 12	NP_001122068.2	Q8N9U0-1
	TC2N	NM_001128595.3		c.904C>A	p.Leu302Ile	missense	Exon 9 of 12	NP_001122067.2	Q8N9U0-1
	TC2N	NM_152332.6		c.904C>A	p.Leu302Ile	missense	Exon 9 of 12	NP_689545.2	Q8N9U0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TC2N	ENST00000435962.7	TSL:2 MANE Select	c.904C>A	p.Leu302Ile	missense	Exon 9 of 12	ENSP00000387882.2	Q8N9U0-1
	TC2N	ENST00000340892.9	TSL:1	c.904C>A	p.Leu302Ile	missense	Exon 9 of 12	ENSP00000343199.5	Q8N9U0-1
	TC2N	ENST00000360594.9	TSL:1	c.904C>A	p.Leu302Ile	missense	Exon 9 of 12	ENSP00000353802.5	Q8N9U0-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1444550 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 718426

African (AFR) AF: 0.00 AC: 0 AN: 33202

American (AMR) AF: 0.00 AC: 0 AN: 44246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25718

East Asian (EAS) AF: 0.00 AC: 0 AN: 39486

South Asian (SAS) AF: 0.00 AC: 0 AN: 82878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 9.08e-7 AC: 1 AN: 1101152

Other (OTH) AF: 0.0000168 AC: 1 AN: 59550

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	Benign	0.12
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.090	T
Eigen	Benign	0.046
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.9	M
PhyloP100		4.9
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.32
Sift	Benign	0.10	T
Sift4G	Benign	0.21	T
Polyphen		0.79	P
Vest4		0.34
MutPred		0.40		Gain of catalytic residue at L307 (P = 0.0523)
MVP		0.56
MPC		0.27
ClinPred		0.81	D
GERP RS		3.8
Varity_R		0.12
gMVP		0.29
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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

hg19: chr14-92258854;