rs10133762

chr14-91826425-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001128596.3(TC2N):c.-56-12600A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 151,510 control chromosomes in the GnomAD database, including 17,756 homozygotes. 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: 𝑓 0.47 (17756 hom., cov: 29)
• Consequence: TC2N NM_001128596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TC2N	NM_001128596.3	c.-56-12600A>C		intron_variant		ENST00000435962.7
TC2N	NM_001128595.3	c.-57+9946A>C		intron_variant
TC2N	NM_001289134.2	c.-57+9946A>C		intron_variant
TC2N	NM_152332.6	c.-57+9758A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TC2N	ENST00000435962.7	c.-56-12600A>C		intron_variant		2	NM_001128596.3	P1
TC2N	ENST00000340892.9	c.-57+9758A>C		intron_variant		1		P1
TC2N	ENST00000360594.9	c.-57+9946A>C		intron_variant		1		P1
TC2N	ENST00000556018.5	c.-57+9946A>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70737 AN: 151396 Hom.: 17759 Cov.: 29

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.491

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.467 AC: 70744 AN: 151510 Hom.: 17756 Cov.: 29 AF XY: 0.467 AC XY: 34570 AN XY: 74038

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.487

Alfa AF: 0.507 Hom.: 4613

Bravo AF: 0.464

Asia WGS AF: 0.427 AC: 1480 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.0
Dann	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs10133762; hg19: chr14-92292769;