rs6053666

chr20-648246-T-C

Variant summary

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

The NM_080725.3(SRXN1):c.*468A>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 0.364 in 456,294 control chromosomes in the GnomAD database, including 32,013 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 0.39 (12364 hom., cov: 32)
  • Exomes 𝑓: 0.35 (19649 hom.)
• Consequence: SRXN1 NM_080725.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

Genes affected

SRXN1 (HGNC:16132): (sulfiredoxin 1) Enables oxidoreductase activity, acting on a sulfur group of donors. Involved in response to oxidative stress. Located in cytosol. [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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRXN1	NM_080725.3	c.*468A>G		3_prime_UTR_variant	2/2	ENST00000381962.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRXN1	ENST00000381962.4	c.*468A>G		3_prime_UTR_variant	2/2	1	NM_080725.3	P1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59114 AN: 151922 Hom.: 12346 Cov.: 32

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.363

GnomAD3 exomes AF: 0.352 AC: 45277 AN: 128530 Hom.: 8441 AF XY: 0.356 AC XY: 25021 AN XY: 70378

Gnomad AFR exome AF: 0.536

Gnomad AMR exome AF: 0.248

Gnomad ASJ exome AF: 0.389

Gnomad EAS exome AF: 0.452

Gnomad SAS exome AF: 0.410

Gnomad FIN exome AF: 0.377

Gnomad NFE exome AF: 0.325

Gnomad OTH exome AF: 0.339

GnomAD4 exome AF: 0.351 AC: 106858 AN: 304254 Hom.: 19649 Cov.: 0 AF XY: 0.357 AC XY: 61826 AN XY: 173210

Gnomad4 AFR exome AF: 0.540

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.379

Gnomad4 EAS exome AF: 0.456

Gnomad4 SAS exome AF: 0.414

Gnomad4 FIN exome AF: 0.367

Gnomad4 NFE exome AF: 0.325

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome AF: 0.389 AC: 59160 AN: 152040 Hom.: 12364 Cov.: 32 AF XY: 0.386 AC XY: 28706 AN XY: 74334

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.362

Alfa AF: 0.346 Hom.: 7288

Bravo AF: 0.386

Asia WGS AF: 0.403 AC: 1401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	3.5
Dann	Benign	0.50

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: rs6053666; hg19: chr20-628890;