22-30627204-A-G

Position:

• chr22-30627204-A-G

Variant summary

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

The NM_000355.4(TCN2):​c.*683A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 160,566 control chromosomes in the GnomAD database, including 16,816 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 0.45 (15936 hom., cov: 34)
  • Exomes 𝑓: 0.43 (880 hom.)
• Consequence: TCN2 NM_000355.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCN2	NM_000355.4	c.*683A>G		3_prime_UTR_variant	9/9	ENST00000215838.8	NP_000346.2
TCN2	NM_001184726.2	c.*683A>G		3_prime_UTR_variant	9/9		NP_001171655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCN2	ENST00000215838.8	c.*683A>G		3_prime_UTR_variant	9/9	1	NM_000355.4	ENSP00000215838.3

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68103 AN: 151972 Hom.: 15923 Cov.: 34

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.494

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.460

GnomAD4 exome AF: 0.426 AC: 3609 AN: 8476 Hom.: 880 Cov.: 0 AF XY: 0.415 AC XY: 1828 AN XY: 4408

Gnomad4 AFR exome AF: 0.208

Gnomad4 AMR exome AF: 0.444

Gnomad4 ASJ exome AF: 0.611

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.472

Gnomad4 OTH exome AF: 0.470

GnomAD4 genome AF: 0.448 AC: 68134 AN: 152090 Hom.: 15936 Cov.: 34 AF XY: 0.450 AC XY: 33439 AN XY: 74344

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.455

Alfa AF: 0.474 Hom.: 2142

Bravo AF: 0.434

Asia WGS AF: 0.306 AC: 1066 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.65

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: rs1544468; hg19: chr22-31023191;