dbSNP rs1982528: SFSWAP:p.Leu421Gln (chr12-131753303-T-A) – 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_004592.4(SFSWAP):c.1262T>A(p.Leu421Gln) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SFSWAP
NM_004592.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.24

Publications

24 publications found

Variant links:

Genes affected

SFSWAP (HGNC:10790): (splicing factor SWAP) This gene encodes a human homolog of Drosophila splicing regulatory protein. This gene autoregulates its expression by control of splicing of its first two introns. In addition, it also regulates the splicing of fibronectin and CD45 genes. Two transcript variants encoding different isoforms have been identified. [provided by RefSeq, May 2012]

SFSWAP 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=0.083826244).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004592.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFSWAP	NM_004592.4	MANE Select	c.1262T>A	p.Leu421Gln	missense	Exon 8 of 18	NP_004583.2
	SFSWAP	NM_001261411.2		c.1262T>A	p.Leu421Gln	missense	Exon 8 of 19	NP_001248340.1	Q12872-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SFSWAP	ENST00000261674.9	TSL:1 MANE Select	c.1262T>A	p.Leu421Gln	missense	Exon 8 of 18	ENSP00000261674.4	Q12872-1
SFSWAP	ENST00000541286.5	TSL:1	c.1262T>A	p.Leu421Gln	missense	Exon 8 of 19	ENSP00000437738.1	Q12872-2
SFSWAP	ENST00000535236.5	TSL:1	n.4596T>A		non_coding_transcript_exon	Exon 6 of 12

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461302

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727008

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111484

Other (OTH)

AF:

0.00

AC:

AN:

60366

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.050

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.34

M_CAP

Benign

0.016

MetaRNN

Benign

0.084

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

2.2

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.70

REVEL

Benign

0.099

Sift

Benign

0.057

Sift4G

Uncertain

0.047

Polyphen

0.0040

Vest4

0.11

MutPred

0.21

Gain of catalytic residue at P422 (P = 5e-04)

MVP

0.068

MPC

0.46

ClinPred

0.21

GERP RS

5.4

PromoterAI

0.026

Neutral

(source)

Varity_R

0.063

gMVP

0.46

Mutation Taster

=96/4

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