12-131753303-T-C

Variant names:

• chr12-131753303-T-C
• rs1982528
• NM_004592.4:c.1262T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004592.4(SFSWAP):​c.1262T>C​(p.Leu421Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.973 in 1,613,468 control chromosomes in the GnomAD database, including 764,458 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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: 𝑓 0.93 (66800 hom., cov: 31)
  • Exomes 𝑓: 0.98 (697658 hom.)
• Consequence: SFSWAP NM_004592.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24
• Publications: 24 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.3489944E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFSWAP	NM_004592.4	c.1262T>C	p.Leu421Pro	missense_variant	Exon 8 of 18	ENST00000261674.9	NP_004583.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFSWAP	ENST00000261674.9	c.1262T>C	p.Leu421Pro	missense_variant	Exon 8 of 18	1	NM_004592.4	ENSP00000261674.4

Frequencies

GnomAD3 genomes AF: 0.934 AC: 142012 AN: 152074 Hom.: 66753 Cov.: 31

Gnomad AFR AF: 0.817

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.962

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.980

Gnomad OTH AF: 0.929

GnomAD2 exomes AF: 0.967 AC: 242988 AN: 251356 AF XY: 0.969

Gnomad AFR exome AF: 0.815

Gnomad AMR exome AF: 0.975

Gnomad ASJ exome AF: 0.936

Gnomad EAS exome AF: 0.993

Gnomad FIN exome AF: 0.996

Gnomad NFE exome AF: 0.978

Gnomad OTH exome AF: 0.964

GnomAD4 exome AF: 0.977 AC: 1427265 AN: 1461276 Hom.: 697658 Cov.: 43 AF XY: 0.977 AC XY: 710176 AN XY: 727000

African (AFR) AF: 0.812 AC: 27189 AN: 33466

American (AMR) AF: 0.973 AC: 43509 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.935 AC: 24445 AN: 26132

East Asian (EAS) AF: 0.993 AC: 39420 AN: 39700

South Asian (SAS) AF: 0.971 AC: 83739 AN: 86242

European-Finnish (FIN) AF: 0.997 AC: 53233 AN: 53418

Middle Eastern (MID) AF: 0.924 AC: 5328 AN: 5766

European-Non Finnish (NFE) AF: 0.983 AC: 1092239 AN: 1111462

Other (OTH) AF: 0.964 AC: 58163 AN: 60366

GnomAD4 genome AF: 0.934 AC: 142116 AN: 152192 Hom.: 66800 Cov.: 31 AF XY: 0.936 AC XY: 69646 AN XY: 74404

African (AFR) AF: 0.818 AC: 33902 AN: 41470

American (AMR) AF: 0.962 AC: 14724 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3257 AN: 3472

East Asian (EAS) AF: 0.992 AC: 5118 AN: 5160

South Asian (SAS) AF: 0.971 AC: 4696 AN: 4834

European-Finnish (FIN) AF: 0.997 AC: 10587 AN: 10616

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.980 AC: 66689 AN: 68026

Other (OTH) AF: 0.929 AC: 1961 AN: 2110

Alfa AF: 0.961 Hom.: 130855

Bravo AF: 0.926

TwinsUK AF: 0.985 AC: 3654

ALSPAC AF: 0.983 AC: 3790

ESP6500AA AF: 0.825 AC: 3636

ESP6500EA AF: 0.978 AC: 8413

ExAC AF: 0.964 AC: 117043

Asia WGS AF: 0.977 AC: 3400 AN: 3478

EpiCase AF: 0.972

EpiControl AF: 0.973

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.040
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.46
DEOGEN2	Benign	0.036	T;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.041	T;T
MetaRNN	Benign	6.3e-7	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.0	N;N
PhyloP100		2.2
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	2.2	N;N
REVEL	Benign	0.12
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.10
MPC		0.71
ClinPred		0.012	T
GERP RS		5.4
PromoterAI		0.010	Neutral
Varity_R		0.063
gMVP		0.38
Mutation Taster		=99/1	polymorphism (auto)

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: rs1982528; hg19: chr12-132237848; COSMIC: COSV107232685; COSMIC: COSV107232685;