Variant 22-30622830-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000355.4(TCN2):c.1107-138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 827,208 control chromosomes in the GnomAD database, including 61,310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10073 hom., cov: 31)

Exomes 𝑓: 0.38 ( 51237 hom. )

Consequence

TCN2
NM_000355.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.92

Variant links:

Genes affected

TCN2 (HGNC:11653): (transcobalamin 2) This gene encodes a member of the vitamin B12-binding protein family. This family of proteins, alternatively referred to as R binders, is expressed in various tissues and secretions. This plasma protein binds cobalamin and mediates the transport of cobalamin into cells. This protein and other mammalian cobalamin-binding proteins, such as transcobalamin I and gastric intrisic factor, may have evolved by duplication of a common ancestral gene. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

TCN2 links:

TCN2 (HGNC:):

TCN2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 22-30622830-C-T is Benign according to our data. Variant chr22-30622830-C-T is described in ClinVar as [Benign]. Clinvar id is 1267520.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCN2	NM_000355.4 linkuse as main transcript	c.1107-138C>T		intron_variant		ENST00000215838.8	NP_000346.2	P20062-1
TCN2	NM_001184726.2 linkuse as main transcript	c.1026-138C>T		intron_variant			NP_001171655.1	P20062-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCN2	ENST00000215838.8 linkuse as main transcript	c.1107-138C>T		intron_variant		1	NM_000355.4	ENSP00000215838.3		P20062-1

Frequencies

GnomAD3 genomes

AF:

0.355

AC:

53932

AN:

151860

Hom.:

10071

Cov.:

show subpopulations

Gnomad AFR

AF:

0.251

Gnomad AMI

AF:

0.460

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.447

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.266

Gnomad FIN

AF:

0.449

Gnomad MID

AF:

0.365

Gnomad NFE

AF:

0.419

Gnomad OTH

AF:

0.371

GnomAD4 exome

AF:

0.381

AC:

257212

AN:

675230

Hom.:

51237

AF XY:

0.378

AC XY:

135549

AN XY:

358684

show subpopulations

Gnomad4 AFR exome

AF:

0.255

Gnomad4 AMR exome

AF:

0.312

Gnomad4 ASJ exome

AF:

0.445

Gnomad4 EAS exome

AF:

0.197

Gnomad4 SAS exome

AF:

0.270

Gnomad4 FIN exome

AF:

0.455

Gnomad4 NFE exome

AF:

0.413

Gnomad4 OTH exome

AF:

0.385

GnomAD4 genome

AF:

0.355

AC:

53938

AN:

151978

Hom.:

10073

Cov.:

AF XY:

0.353

AC XY:

26228

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.251

Gnomad4 AMR

AF:

0.342

Gnomad4 ASJ

AF:

0.447

Gnomad4 EAS

AF:

0.193

Gnomad4 SAS

AF:

0.266

Gnomad4 FIN

AF:

0.449

Gnomad4 NFE

AF:

0.419

Gnomad4 OTH

AF:

0.366

Alfa

AF:

0.378

Hom.:

1380

Bravo

AF:

0.344

Asia WGS

AF:

0.264

AC:

920

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.17

DANN

Benign

0.43

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over