chr14-91827174-A-G

Position:

• chr14-91827174-A-G

Variant summary

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

The NM_001128596.3(TC2N):​c.-56-13349T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 151,914 control chromosomes in the GnomAD database, including 23,185 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 0.55 (23185 hom., cov: 32)
• Consequence: TC2N NM_001128596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TC2N	NM_001128596.3	c.-56-13349T>C		intron_variant		ENST00000435962.7	NP_001122068.2
TC2N	NM_001128595.3	c.-57+9197T>C		intron_variant			NP_001122067.2
TC2N	NM_001289134.2	c.-57+9197T>C		intron_variant			NP_001276063.2
TC2N	NM_152332.6	c.-57+9009T>C		intron_variant			NP_689545.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TC2N	ENST00000435962.7	c.-56-13349T>C		intron_variant		2	NM_001128596.3	ENSP00000387882	P1
TC2N	ENST00000340892.9	c.-57+9009T>C		intron_variant		1		ENSP00000343199	P1
TC2N	ENST00000360594.9	c.-57+9197T>C		intron_variant		1		ENSP00000353802	P1
TC2N	ENST00000556018.5	c.-57+9197T>C		intron_variant		2		ENSP00000451317

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83515 AN: 151796 Hom.: 23182 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.550 AC: 83554 AN: 151914 Hom.: 23185 Cov.: 32 AF XY: 0.547 AC XY: 40646 AN XY: 74240

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.552

Alfa AF: 0.566 Hom.: 11893

Bravo AF: 0.554

Asia WGS AF: 0.509 AC: 1771 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.93

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: rs2402074; hg19: chr14-92293518;