Genetic Variant SFPQ:p.Gln253His (chr1-35192291-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_005066.3(SFPQ):c.759G>C(p.Gln253His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000153 in 1,309,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

SFPQ
NM_005066.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00200

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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34533757).

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.759G>C	p.Gln253His	missense	Exon 1 of 10	NP_005057.1	P23246-1
SFPQ	NR_136702.2		n.855G>C		non_coding_transcript_exon	Exon 1 of 12
SFPQ	NR_136703.2		n.855G>C		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.759G>C	p.Gln253His	missense	Exon 1 of 10	ENSP00000349748.5	P23246-1
	SFPQ	ENST00000696553.1		c.822G>C	p.Gln274His	missense	Exon 1 of 10	ENSP00000512713.1	A0A8Q3WMA7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000153

AC:

AN:

1309726

Hom.:

Cov.:

AF XY:

0.00000155

AC XY:

AN XY:

646520

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26044

American (AMR)

AF:

0.00

AC:

AN:

23256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23040

East Asian (EAS)

AF:

0.00

AC:

AN:

27514

South Asian (SAS)

AF:

0.00

AC:

AN:

71908

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4018

European-Non Finnish (NFE)

AF:

0.00000191

AC:

AN:

1047188

Other (OTH)

AF:

0.00

AC:

AN:

54140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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

Benign

0.16

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.044

Eigen

Benign

0.094

Eigen_PC

Benign

0.059

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.55

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.35

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

0.0020

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-1.3

REVEL

Benign

0.11

Sift4G

Benign

0.11

Polyphen

0.98

Vest4

0.42

MutPred

0.13

Loss of glycosylation at P249 (P = 0.1589)

MVP

0.89

MPC

0.89

ClinPred

0.51

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.23

gMVP

0.28

Mutation Taster

=85/15

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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