Genetic Variant SFPQ:p.Met212Ile (chr1-35192414-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005066.3(SFPQ):c.636G>A(p.Met212Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SFPQ
NM_005066.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19202253).

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.636G>A	p.Met212Ile	missense	Exon 1 of 10	NP_005057.1	P23246-1
SFPQ	NR_136702.2		n.732G>A		non_coding_transcript_exon	Exon 1 of 12
SFPQ	NR_136703.2		n.732G>A		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.636G>A	p.Met212Ile	missense	Exon 1 of 10	ENSP00000349748.5	P23246-1
	SFPQ	ENST00000696553.1		c.699G>A	p.Met233Ile	missense	Exon 1 of 10	ENSP00000512713.1	A0A8Q3WMA7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1274280

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

626286

African (AFR)

AF:

0.00

AC:

AN:

25210

American (AMR)

AF:

0.00

AC:

AN:

18444

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20590

East Asian (EAS)

AF:

0.00

AC:

AN:

27678

South Asian (SAS)

AF:

0.00

AC:

AN:

65038

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31010

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3830

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1029816

Other (OTH)

AF:

0.00

AC:

AN:

52664

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.036

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.53

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

PhyloP100

2.0

PrimateAI

Pathogenic

0.97

PROVEAN

Benign

-0.58

REVEL

Benign

0.070

Sift4G

Benign

0.49

Polyphen

0.046

Vest4

0.30

MutPred

0.30

Gain of ubiquitination at K211 (P = 0.1575)

MVP

0.34

MPC

1.0

ClinPred

0.92

GERP RS

3.7

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.46

gMVP

0.13

Mutation Taster

=91/9

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over