rs10493066

Positions:

• chr1-35180524-C-T

Variant summary

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

The ENST00000468598.5(SFPQ):​n.122G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0724 in 1,049,484 control chromosomes in the GnomAD database, including 16,290 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 0.23 (8834 hom., cov: 32)
  • Exomes 𝑓: 0.045 (7456 hom.)
• Consequence: SFPQ ENST00000468598.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152

Genes affected

SFPQ (HGNC:10774): (splicing factor proline and glutamine rich) Enables DNA binding activity; histone deacetylase binding activity; and protein homodimerization activity. Involved in several processes, including alternative mRNA splicing, via spliceosome; positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; and regulation of transcription by RNA polymerase II. Acts upstream of or within double-strand break repair via homologous recombination. Located in chromatin; nuclear matrix; and paraspeckles. [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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFPQ	XM_017002053.3	c.*3932G>A		3_prime_UTR_variant	10/12
SFPQ	XM_017002054.3	c.*3932G>A		3_prime_UTR_variant	10/12
SFPQ	XM_005271112.6	c.*3321+611G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFPQ	ENST00000468598.5	n.122G>A		non_coding_transcript_exon_variant	1/3	1
SFPQ	ENST00000460428.5	c.242-2488G>A		intron_variant, NMD_transcript_variant		2
SFPQ	ENST00000470472.5	c.649-2488G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35301 AN: 151954 Hom.: 8799 Cov.: 32

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0224

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.0452 AC: 40535 AN: 897412 Hom.: 7456 Cov.: 33 AF XY: 0.0430 AC XY: 17826 AN XY: 414494

Gnomad4 AFR exome AF: 0.602

Gnomad4 AMR exome AF: 0.340

Gnomad4 ASJ exome AF: 0.0337

Gnomad4 EAS exome AF: 0.695

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.0994

Gnomad4 NFE exome AF: 0.0165

Gnomad4 OTH exome AF: 0.102

GnomAD4 genome AF: 0.233 AC: 35407 AN: 152072 Hom.: 8834 Cov.: 32 AF XY: 0.238 AC XY: 17689 AN XY: 74328

Gnomad4 AFR AF: 0.564

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.0224

Gnomad4 OTH AF: 0.207

Alfa AF: 0.0635 Hom.: 3119

Bravo AF: 0.266

Asia WGS AF: 0.410 AC: 1425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10493066; hg19: chr1-35646125;