chr22-36467627-CCT-C

Position:

• chr22-36467627-CCT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_012473.4(TXN2):​c.*175_*176del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 601,880 control chromosomes in the GnomAD database, including 367 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (89 hom., cov: 32)
  • Exomes 𝑓: 0.030 (278 hom.)
• Consequence: TXN2 NM_012473.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.314

Genes affected

TXN2 (HGNC:17772): (thioredoxin 2) This nuclear gene encodes a mitochondrial member of the thioredoxin family, a group of small multifunctional redox-active proteins. The encoded protein may play important roles in the regulation of the mitochondrial membrane potential and in protection against oxidant-induced apoptosis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 22-36467627-CCT-C is Benign according to our data. Variant chr22-36467627-CCT-C is described in ClinVar as [Benign]. Clinvar id is 1222057.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0261 (3979/152322) while in subpopulation NFE AF= 0.042 (2855/68018). AF 95% confidence interval is 0.0407. There are 89 homozygotes in gnomad4. There are 2009 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 89 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXN2	NM_012473.4	c.*175_*176del		3_prime_UTR_variant	4/4	ENST00000216185.7
TXN2	XM_006724226.2	c.*175_*176del		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXN2	ENST00000216185.7	c.*175_*176del		3_prime_UTR_variant	4/4	1	NM_012473.4	P1
TXN2	ENST00000403313.5	c.*175_*176del		3_prime_UTR_variant	4/4	3		P1
TXN2	ENST00000416967.1	c.*175_*176del		3_prime_UTR_variant	4/4	2
TXN2	ENST00000487725.1	n.656_657del		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes AF: 0.0261 AC: 3980 AN: 152204 Hom.: 89 Cov.: 32

Gnomad AFR AF: 0.00596

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00620

Gnomad FIN AF: 0.0494

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0420

Gnomad OTH AF: 0.0224

GnomAD4 exome AF: 0.0302 AC: 13573 AN: 449558 Hom.: 278 AF XY: 0.0287 AC XY: 6842 AN XY: 238098

Gnomad4 AFR exome AF: 0.00539

Gnomad4 AMR exome AF: 0.0114

Gnomad4 ASJ exome AF: 0.00644

Gnomad4 EAS exome AF: 0.0000670

Gnomad4 SAS exome AF: 0.00525

Gnomad4 FIN exome AF: 0.0520

Gnomad4 NFE exome AF: 0.0400

Gnomad4 OTH exome AF: 0.0265

GnomAD4 genome AF: 0.0261 AC: 3979 AN: 152322 Hom.: 89 Cov.: 32 AF XY: 0.0270 AC XY: 2009 AN XY: 74484

Gnomad4 AFR AF: 0.00594

Gnomad4 AMR AF: 0.0129

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00600

Gnomad4 FIN AF: 0.0494

Gnomad4 NFE AF: 0.0420

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.0428 Hom.: 29

Bravo AF: 0.0215

Asia WGS AF: 0.00375 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs148887681; hg19: chr22-36863674;