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GeneBe

1-35190780-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005066.3(SFPQ):c.1233A>G(p.Thr411=) 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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.343 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 436 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SFPQNM_005066.3 linkuse as main transcriptc.1233A>G p.Thr411= synonymous_variant 3/10 ENST00000357214.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SFPQENST00000357214.6 linkuse as main transcriptc.1233A>G p.Thr411= synonymous_variant 3/101 NM_005066.3 P1P23246-1
SFPQENST00000696553.1 linkuse as main transcriptc.1296A>G p.Thr432= synonymous_variant 3/10

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00286
AC:
436
AN:
152236
Hom.:
4
Cov.:
33
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.:
0
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.:
6
Cov.:
32
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00286
AC:
436
AN:
152354
Hom.:
4
Cov.:
33
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.:
1
Bravo
AF:
0.00305
EpiCase
AF:
0.00322
EpiControl
AF:
0.00338

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeSep 05, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
Cadd
Benign
11
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.

Other links and lift over

dbSNP: rs149880317; hg19: chr1-35656381; COSMIC: COSV100599543; COSMIC: COSV100599543; API