rs6053666

Variant names:

• chr20-648246-T-C
• rs6053666
• NM_080725.3:c.*468A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate 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
• Publications: 19 publications found

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]

ENSG00000270299 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.101).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080725.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRXN1	NM_080725.3	MANE Select	c.*468A>G		3_prime_UTR	Exon 2 of 2	NP_542763.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRXN1	ENST00000381962.4	TSL:1 MANE Select	c.*468A>G		3_prime_UTR	Exon 2 of 2	ENSP00000371388.4
	ENSG00000270299	ENST00000488788.2	TSL:2	c.*610A>G		3_prime_UTR	Exon 3 of 3	ENSP00000474279.1
	SRXN1	ENST00000918016.1		c.*468A>G		3_prime_UTR	Exon 2 of 2	ENSP00000588075.1

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

GnomAD2 exomes AF: 0.352 AC: 45277 AN: 128530 AF XY: 0.356

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 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

African (AFR) AF: 0.540 AC: 4664 AN: 8644

American (AMR) AF: 0.250 AC: 6811 AN: 27290

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 4091 AN: 10804

East Asian (EAS) AF: 0.456 AC: 4199 AN: 9216

South Asian (SAS) AF: 0.414 AC: 24732 AN: 59748

European-Finnish (FIN) AF: 0.367 AC: 4544 AN: 12380

Middle Eastern (MID) AF: 0.356 AC: 992 AN: 2784

European-Non Finnish (NFE) AF: 0.325 AC: 51764 AN: 159120

Other (OTH) AF: 0.355 AC: 5061 AN: 14268

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

African (AFR) AF: 0.541 AC: 22422 AN: 41466

American (AMR) AF: 0.275 AC: 4196 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1260 AN: 3466

East Asian (EAS) AF: 0.449 AC: 2321 AN: 5172

South Asian (SAS) AF: 0.407 AC: 1956 AN: 4810

European-Finnish (FIN) AF: 0.370 AC: 3919 AN: 10580

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21930 AN: 67944

Other (OTH) AF: 0.362 AC: 765 AN: 2116

Alfa AF: 0.349 Hom.: 22538

Bravo AF: 0.386

Asia WGS AF: 0.403 AC: 1401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.5
DANN	Benign	0.50
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6053666; hg19: chr20-628890;