chr14-91792510-G-T

Position:

• chr14-91792510-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TC2N	NM_001128596.3	c.904C>A	p.Leu302Ile	missense_variant	9/12	ENST00000435962.7	NP_001122068.2
TC2N	NM_001128595.3	c.904C>A	p.Leu302Ile	missense_variant	9/12		NP_001122067.2
TC2N	NM_152332.6	c.904C>A	p.Leu302Ile	missense_variant	9/12		NP_689545.2
TC2N	NM_001289134.2	c.856-4883C>A		intron_variant			NP_001276063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TC2N	ENST00000435962.7	c.904C>A	p.Leu302Ile	missense_variant	9/12	2	NM_001128596.3	ENSP00000387882.2

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.08e-7

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 24, 2024

The c.904C>A (p.L302I) alteration is located in exon 9 (coding exon 8) of the TC2N gene. This alteration results from a C to A substitution at nucleotide position 904, causing the leucine (L) at amino acid position 302 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;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;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.9	M;M;M;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.10	T;T;T;T
Sift4G	Benign	0.21	T;T;T;T
Polyphen		0.79	P;P;P;.
Vest4		0.34
MutPred		0.40		Gain of catalytic residue at L307 (P = 0.0523);Gain of catalytic residue at L307 (P = 0.0523);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-92258854;