22-36468016-G-T

Position:

• chr22-36468016-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_012473.4(TXN2):​c.388-99C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 1,019,874 control chromosomes in the GnomAD database, including 619 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (93 hom., cov: 32)
  • Exomes 𝑓: 0.031 (526 hom.)
• Consequence: TXN2 NM_012473.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.197

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 22-36468016-G-T is Benign according to our data. Variant chr22-36468016-G-T is described in ClinVar as [Benign]. Clinvar id is 1271118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0261 (3972/152170) while in subpopulation NFE AF= 0.042 (2854/67980). AF 95% confidence interval is 0.0407. There are 93 homozygotes in gnomad4. There are 1993 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 93 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXN2	NM_012473.4	c.388-99C>A		intron_variant		ENST00000216185.7
TXN2	XM_006724226.2	c.388-99C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXN2	ENST00000216185.7	c.388-99C>A		intron_variant		1	NM_012473.4	P1

Frequencies

GnomAD3 genomes AF: 0.0261 AC: 3973 AN: 152052 Hom.: 93 Cov.: 32

Gnomad AFR AF: 0.00585

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00560

Gnomad FIN AF: 0.0499

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0420

Gnomad OTH AF: 0.0215

GnomAD4 exome AF: 0.0307 AC: 26632 AN: 867704 Hom.: 526 AF XY: 0.0300 AC XY: 13501 AN XY: 449602

Gnomad4 AFR exome AF: 0.00456

Gnomad4 AMR exome AF: 0.00919

Gnomad4 ASJ exome AF: 0.0117

Gnomad4 EAS exome AF: 0.0000566

Gnomad4 SAS exome AF: 0.00508

Gnomad4 FIN exome AF: 0.0518

Gnomad4 NFE exome AF: 0.0376

Gnomad4 OTH exome AF: 0.0254

GnomAD4 genome AF: 0.0261 AC: 3972 AN: 152170 Hom.: 93 Cov.: 32 AF XY: 0.0268 AC XY: 1993 AN XY: 74390

Gnomad4 AFR AF: 0.00583

Gnomad4 AMR AF: 0.0117

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00540

Gnomad4 FIN AF: 0.0499

Gnomad4 NFE AF: 0.0420

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0300 Hom.: 25

Bravo AF: 0.0214

Asia WGS AF: 0.00346 AC: 13 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.4
DANN	Benign	0.80

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: rs73169632; hg19: chr22-36864063;