19-49646584-C-A

Variant names:

• chr19-49646584-C-A
• NM_021228.3:c.320C>A

Variant summary

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

The NM_021228.3(SCAF1):​c.320C>A​(p.Pro107Gln) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCAF1 NM_021228.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61

Genes affected

SCAF1 (HGNC:30403): (SR-related CTD associated factor 1) Enables RNA polymerase II C-terminal domain binding activity. Predicted to be involved in RNA splicing; mRNA processing; and transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.22972691).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAF1	NM_021228.3	c.320C>A	p.Pro107Gln	missense_variant	Exon 5 of 11	ENST00000360565.8	NP_067051.2
SCAF1	XM_011527194.4	c.329C>A	p.Pro110Gln	missense_variant	Exon 5 of 11		XP_011525496.1
SCAF1	XM_005259122.6	c.320C>A	p.Pro107Gln	missense_variant	Exon 5 of 11		XP_005259179.1
SCAF1	XM_017027083.3	c.50C>A	p.Pro17Gln	missense_variant	Exon 2 of 8		XP_016882572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAF1	ENST00000360565.8	c.320C>A	p.Pro107Gln	missense_variant	Exon 5 of 11	2	NM_021228.3	ENSP00000353769.2
SCAF1	ENST00000598359.5	c.320C>A	p.Pro107Gln	missense_variant	Exon 5 of 7	3		ENSP00000473210.1
SCAF1	ENST00000595242.3	c.324C>A	p.Pro108Pro	synonymous_variant	Exon 4 of 4	3		ENSP00000472276.1
SCAF1	ENST00000601038.5	c.*26C>A		downstream_gene_variant		3		ENSP00000472649.1

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 specified Uncertain:1

Mar 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.320C>A (p.P107Q) alteration is located in exon 5 (coding exon 4) of the SCAF1 gene. This alteration results from a C to A substitution at nucleotide position 320, causing the proline (P) at amino acid position 107 to be replaced by a glutamine (Q). 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	0.26
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Benign	0.92
DEOGEN2	Benign	0.052	T;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.58	T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.4	N;.
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D;.
Sift4G	Benign	0.072	T;D
Polyphen		1.0	D;.
Vest4		0.60
MutPred		0.48		Loss of catalytic residue at P106 (P = 0.0131);Loss of catalytic residue at P106 (P = 0.0131);
MVP		0.12
MPC		0.59
ClinPred		0.74	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.39

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: chr19-50149841;