Genetic Variant SFPQ:p.Thr411Thr (chr1-35190780-T-C) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005066.3(SFPQ):c.1233A>G(p.Thr411Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00288 in 1,614,242 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0029 ( 6 hom. )

Consequence

SFPQ
NM_005066.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.343

Variant links:

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]

SFPQ links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 1-35190780-T-C is Benign according to our data. Variant chr1-35190780-T-C is described in ClinVar as [Benign]. Clinvar id is 712023.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.343 with no splicing effect.

BS2

High AC in GnomAd4 at 436 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFPQ	NM_005066.3 link	c.1233A>G	p.Thr411Thr	synonymous_variant	Exon 3 of 10	ENST00000357214.6	NP_005057.1	P23246-1A0A384N5Z8Q86VG2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SFPQ	ENST00000357214.6 link	c.1233A>G	p.Thr411Thr	synonymous_variant	Exon 3 of 10	1	NM_005066.3	ENSP00000349748.5	P23246-1
SFPQ	ENST00000696553.1 link	c.1296A>G	p.Thr432Thr	synonymous_variant	Exon 3 of 10			ENSP00000512713.1	A0A8Q3WMA7
SFPQ	ENST00000470472.5 link	n.-206A>G		upstream_gene_variant		5		ENSP00000424440.1	H0Y9K7

Frequencies

GnomAD3 genomes

AF:

0.00286

AC:

436

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.0239

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00304

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00286

AC:

718

AN:

251416

Hom.:

AF XY:

0.00271

AC XY:

368

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.00477

Gnomad ASJ exome

AF:

0.0183

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00289

Gnomad OTH exome

AF:

0.00456

GnomAD4 exome

AF:

0.00288

AC:

4211

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

2049

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00487

Gnomad4 ASJ exome

AF:

0.0186

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000168

Gnomad4 NFE exome

AF:

0.00293

Gnomad4 OTH exome

AF:

0.00361

GnomAD4 genome

AF:

0.00286

AC:

436

AN:

152354

Hom.:

Cov.:

AF XY:

0.00295

AC XY:

220

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.00765

Gnomad4 ASJ

AF:

0.0239

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00304

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00367

Hom.:

Bravo

AF:

0.00305

EpiCase

AF:

0.00322

EpiControl

AF:

0.00338

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 05, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over