21-31671686-A-G

Position:

• chr21-31671686-A-G

Variant summary

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

The NM_020706.2(SCAF4):​c.3157T>C​(p.Ser1053Pro) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCAF4 NM_020706.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.40

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=0.20565066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAF4	NM_020706.2	c.3157T>C	p.Ser1053Pro	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.3157T>C	p.Ser1053Pro	missense_variant	20/20	1	NM_020706.2	ENSP00000286835.7
SCAF4	ENST00000434667.3	c.3112T>C	p.Ser1038Pro	missense_variant	19/19	1		ENSP00000402377.2
SCAF4	ENST00000399804.5	c.3091T>C	p.Ser1031Pro	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

Jan 03, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter 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	Benign	0.20
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T;.;.
Eigen	Benign	0.11
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.47	N
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.90	L;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.32	N;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.0040	D;D;D
Sift4G	Benign	0.34	T;T;T
Polyphen		1.0	D;B;.
Vest4		0.37
MutPred		0.20		Loss of phosphorylation at S1053 (P = 7e-04);.;.;
MVP		0.52
MPC		0.30
ClinPred		0.59	D
GERP RS		4.7
Varity_R		0.16
gMVP		0.048

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: chr21-33043999;