NM_020706.2:c.3125G>T

Variant names:

• chr21-31671718-C-A
• NM_020706.2:c.3125G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020706.2(SCAF4):​c.3125G>T​(p.Arg1042Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCAF4 NM_020706.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.07
• Publications: 0 publications found

Genes affected

SCAF4 (HGNC:19304): (SR-related CTD associated factor 4) This gene likely encodes a member of the arginine/serine-rich splicing factor family. A similar protein in Rat appears to bind the large subunit of RNA polymerase II and provide a link between transcription and pre-mRNA splicing. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2009]

SCAF4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Franklin by Genoox, Ambry Genetics, ClinGen
• Fliedner-Zweier syndrome

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020706.2. 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
	SCAF4	NM_020706.2	MANE Select	c.3125G>T	p.Arg1042Met	missense	Exon 20 of 20	NP_065757.1	O95104-1
	SCAF4	NM_001145444.1		c.3080G>T	p.Arg1027Met	missense	Exon 19 of 19	NP_001138916.1	O95104-3
	SCAF4	NM_001145445.1		c.3059G>T	p.Arg1020Met	missense	Exon 20 of 20	NP_001138917.1	O95104-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAF4	ENST00000286835.12	TSL:1 MANE Select	c.3125G>T	p.Arg1042Met	missense	Exon 20 of 20	ENSP00000286835.7	O95104-1
	SCAF4	ENST00000434667.3	TSL:1	c.3080G>T	p.Arg1027Met	missense	Exon 19 of 19	ENSP00000402377.2	O95104-3
	SCAF4	ENST00000399804.5	TSL:1	c.3059G>T	p.Arg1020Met	missense	Exon 20 of 20	ENSP00000382703.1	O95104-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	26
DANN	Benign	0.96
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		7.1
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.67
MutPred		0.32		Loss of loop (P = 0.2237)
MVP		0.40
MPC		0.26
ClinPred		0.87	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.31
gMVP		0.23
Mutation Taster		=52/48	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

hg19: chr21-33044031;