chr21-31671496-G-A

Position:

• chr21-31671496-G-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.3347C>T​(p.Ala1116Val) 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. 13/21 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: 3.97

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=0.1430425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAF4	NM_020706.2	c.3347C>T	p.Ala1116Val	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.3347C>T	p.Ala1116Val	missense_variant	20/20	1	NM_020706.2	ENSP00000286835.7
SCAF4	ENST00000434667.3	c.3302C>T	p.Ala1101Val	missense_variant	19/19	1		ENSP00000402377.2
SCAF4	ENST00000399804.5	c.3281C>T	p.Ala1094Val	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

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 24, 2023

The c.3347C>T (p.A1116V) alteration is located in exon 20 (coding exon 20) of the SCAF4 gene. This alteration results from a C to T substitution at nucleotide position 3347, causing the alanine (A) at amino acid position 1116 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T;.;.
Eigen	Benign	0.081
Eigen_PC	Benign	0.085
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.34	N;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.82	N;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.024	D;D;D
Sift4G	Benign	0.20	T;T;T
Polyphen		0.98	D;B;.
Vest4		0.065
MutPred		0.17		Gain of sheet (P = 0.0344);.;.;
MVP		0.28
MPC		0.24
ClinPred		0.46	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.14
gMVP		0.036

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: chr21-33043809;