12-131753227-C-T

Position:

• chr12-131753227-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004592.4(SFSWAP):​c.1186C>T​(p.Leu396Phe) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SFSWAP NM_004592.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.173

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2169581).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFSWAP	NM_004592.4	c.1186C>T	p.Leu396Phe	missense_variant	8/18	ENST00000261674.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFSWAP	ENST00000261674.9	c.1186C>T	p.Leu396Phe	missense_variant	8/18	1	NM_004592.4	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 21, 2024

The c.1186C>T (p.L396F) alteration is located in exon 8 (coding exon 8) of the SFSWAP gene. This alteration results from a C to T substitution at nucleotide position 1186, causing the leucine (L) at amino acid position 396 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	0.030
Eigen_PC	Benign	-0.064
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.0	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.17
Sift	Benign	0.030	D;D
Sift4G	Uncertain	0.046	D;T
Polyphen		0.99	D;.
Vest4		0.36
MutPred		0.25		Gain of catalytic residue at Y392 (P = 0);Gain of catalytic residue at Y392 (P = 0);
MVP		0.21
MPC		1.3
ClinPred		0.54	D
GERP RS		4.5
Varity_R		0.041
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-132237772;