21-31671700-T-A

Variant names:

• chr21-31671700-T-A
• NM_020706.2:c.3143A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020706.2(SCAF4):​c.3143A>T​(p.Glu1048Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 7.13
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15779483).

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.3143A>T	p.Glu1048Val	missense	Exon 20 of 20	NP_065757.1	O95104-1
	SCAF4	NM_001145444.1		c.3098A>T	p.Glu1033Val	missense	Exon 19 of 19	NP_001138916.1	O95104-3
	SCAF4	NM_001145445.1		c.3077A>T	p.Glu1026Val	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.3143A>T	p.Glu1048Val	missense	Exon 20 of 20	ENSP00000286835.7	O95104-1
	SCAF4	ENST00000434667.3	TSL:1	c.3098A>T	p.Glu1033Val	missense	Exon 19 of 19	ENSP00000402377.2	O95104-3
	SCAF4	ENST00000399804.5	TSL:1	c.3077A>T	p.Glu1026Val	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	0.81
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.0072
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.59	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.4	L
PhyloP100		7.1
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.038
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.017	D
Polyphen		0.012	B
Vest4		0.23
MutPred		0.38		Gain of sheet (P = 0.0036)
MVP		0.46
MPC		0.28
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.25
gMVP		0.094
Mutation Taster		=78/22	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: chr21-33044013;