rs1356549098

Variant names:

• chr12-131726961-A-G
• rs1356549098
• NM_004592.4:c.854A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-131726961-A-G
• chr12-131726961-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004592.4(SFSWAP):​c.854A>G​(p.Asn285Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000187 in 1,601,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SFSWAP NM_004592.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.52
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05652532).

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.854A>G	p.Asn285Ser	missense	Exon 6 of 18	NP_004583.2
	SFSWAP	NM_001261411.2		c.854A>G	p.Asn285Ser	missense	Exon 6 of 19	NP_001248340.1	Q12872-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFSWAP	ENST00000261674.9	TSL:1 MANE Select	c.854A>G	p.Asn285Ser	missense	Exon 6 of 18	ENSP00000261674.4	Q12872-1
	SFSWAP	ENST00000541286.5	TSL:1	c.854A>G	p.Asn285Ser	missense	Exon 6 of 19	ENSP00000437738.1	Q12872-2
	SFSWAP	ENST00000535236.5	TSL:1	n.4188A>G		non_coding_transcript_exon	Exon 4 of 12

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152240 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1449414 Hom.: 0 Cov.: 28 AF XY: 0.00000277 AC XY: 2 AN XY: 721368

African (AFR) AF: 0.00 AC: 0 AN: 33064

American (AMR) AF: 0.0000229 AC: 1 AN: 43638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26016

East Asian (EAS) AF: 0.00 AC: 0 AN: 39388

South Asian (SAS) AF: 0.00 AC: 0 AN: 84814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103376

Other (OTH) AF: 0.00 AC: 0 AN: 59962

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152240 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74390

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	19
DANN	Benign	0.25
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.5
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.32	N
REVEL	Benign	0.058
Sift	Benign	0.51	T
Sift4G	Benign	0.50	T
Polyphen		0.037	B
Vest4		0.054
MutPred		0.25		Gain of phosphorylation at N285 (P = 0.0019)
MVP		0.36
MPC		0.66
ClinPred		0.48	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.033
gMVP		0.036
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs1356549098; hg19: chr12-132211506;