21-31671700-T-A

Position:

• chr21-31671700-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

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=0.15779483).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAF4	NM_020706.2	c.3143A>T	p.Glu1048Val	missense_variant	20/20	ENST00000286835.12	NP_065757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAF4	ENST00000286835.12	c.3143A>T	p.Glu1048Val	missense_variant	20/20	1	NM_020706.2	ENSP00000286835.7
SCAF4	ENST00000434667.3	c.3098A>T	p.Glu1033Val	missense_variant	19/19	1		ENSP00000402377.2
SCAF4	ENST00000399804.5	c.3077A>T	p.Glu1026Val	missense_variant	20/20	1		ENSP00000382703.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

May 30, 2024

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

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;D;D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.4	L;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.2	D;D;D
REVEL	Benign	0.038
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.017	D;D;D
Polyphen		0.012	B;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

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: chr21-33044013;