Genetic Variant SFPQ:p.Gly215Trp (chr1-35192407-C-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The NM_005066.3(SFPQ):c.643G>T(p.Gly215Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,272,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G215R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

SFPQ
NM_005066.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.67

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.746

BS2

High AC in GnomAdExome4 at 20 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005066.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SFPQ	NM_005066.3	MANE Select	c.643G>T	p.Gly215Trp	missense	Exon 1 of 10	NP_005057.1	P23246-1
SFPQ	NR_136702.2		n.739G>T		non_coding_transcript_exon	Exon 1 of 12
SFPQ	NR_136703.2		n.739G>T		non_coding_transcript_exon	Exon 1 of 12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFPQ	ENST00000357214.6	TSL:1 MANE Select	c.643G>T	p.Gly215Trp	missense	Exon 1 of 10	ENSP00000349748.5	P23246-1
	SFPQ	ENST00000696553.1		c.706G>T	p.Gly236Trp	missense	Exon 1 of 10	ENSP00000512713.1	A0A8Q3WMA7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1272370

Hom.:

Cov.:

AF XY:

0.0000128

AC XY:

AN XY:

625212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25110

American (AMR)

AF:

0.00

AC:

AN:

18082

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20418

East Asian (EAS)

AF:

0.00

AC:

AN:

27680

South Asian (SAS)

AF:

0.00

AC:

AN:

64658

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30946

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3784

European-Non Finnish (NFE)

AF:

0.0000194

AC:

AN:

1029106

Other (OTH)

AF:

0.00

AC:

AN:

52586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.17

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.59

M_CAP

Pathogenic

0.87

MetaRNN

Pathogenic

0.75

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

2.7

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-1.5

REVEL

Benign

0.11

Sift4G

Uncertain

0.023

Polyphen

0.99

Vest4

0.48

MutPred

0.31

Gain of MoRF binding (P = 0.062)

MVP

0.89

MPC

1.1

ClinPred

1.0

GERP RS

2.6

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.15

gMVP

0.27

Mutation Taster

=82/18

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over