rs10133762

Variant names:

• chr14-91826425-T-G
• rs10133762
• NM_001128596.3:c.-56-12600A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
TC2N	NM_001128596.3	c.-56-12600A>C		intron_variant	Intron 1 of 11	ENST00000435962.7	NP_001122068.2
TC2N	NM_001128595.3	c.-57+9946A>C		intron_variant	Intron 1 of 11		NP_001122067.2
TC2N	NM_152332.6	c.-57+9758A>C		intron_variant	Intron 1 of 11		NP_689545.2
TC2N	NM_001289134.2	c.-57+9946A>C		intron_variant	Intron 1 of 10		NP_001276063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TC2N	ENST00000435962.7	c.-56-12600A>C		intron_variant	Intron 1 of 11	2	NM_001128596.3	ENSP00000387882.2
TC2N	ENST00000340892.9	c.-57+9758A>C		intron_variant	Intron 1 of 11	1		ENSP00000343199.5
TC2N	ENST00000360594.9	c.-57+9946A>C		intron_variant	Intron 1 of 11	1		ENSP00000353802.5
TC2N	ENST00000556018.5	c.-57+9946A>C		intron_variant	Intron 1 of 10	2		ENSP00000451317.1

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

African (AFR) AF: 0.274 AC: 11328 AN: 41344

American (AMR) AF: 0.551 AC: 8400 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1898 AN: 3462

East Asian (EAS) AF: 0.485 AC: 2493 AN: 5136

South Asian (SAS) AF: 0.397 AC: 1901 AN: 4792

European-Finnish (FIN) AF: 0.533 AC: 5558 AN: 10432

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37399 AN: 67786

Other (OTH) AF: 0.487 AC: 1027 AN: 2110

Alfa AF: 0.493 Hom.: 5043

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
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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: rs10133762; hg19: chr14-92292769;