19-49651041-C-T

Position:

• chr19-49651041-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_021228.3(SCAF1):​c.652C>T​(p.Pro218Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 17)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: SCAF1 NM_021228.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.549

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07914367).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAF1	NM_021228.3	c.652C>T	p.Pro218Ser	missense_variant	7/11	ENST00000360565.8	NP_067051.2
SCAF1	XM_011527194.4	c.661C>T	p.Pro221Ser	missense_variant	7/11		XP_011525496.1
SCAF1	XM_005259122.6	c.652C>T	p.Pro218Ser	missense_variant	7/11		XP_005259179.1
SCAF1	XM_017027083.3	c.382C>T	p.Pro128Ser	missense_variant	4/8		XP_016882572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAF1	ENST00000360565.8	c.652C>T	p.Pro218Ser	missense_variant	7/11	2	NM_021228.3	ENSP00000353769.2
SCAF1	ENST00000598359.5	c.*43C>T		downstream_gene_variant		3		ENSP00000473210.1

Frequencies

GnomAD3 genomes Cov.: 17

GnomAD4 exome AF: 0.00000230 AC: 2 AN: 869904 Hom.: 0 Cov.: 13 AF XY: 0.00000230 AC XY: 1 AN XY: 434074

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000304

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 17

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2023

The c.652C>T (p.P218S) alteration is located in exon 7 (coding exon 6) of the SCAF1 gene. This alteration results from a C to T substitution at nucleotide position 652, causing the proline (P) at amino acid position 218 to be replaced by a serine (S). 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	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.51
DEOGEN2	Benign	0.047	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.51	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.030
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.88	T
Polyphen		0.0030	B
Vest4		0.23
MutPred		0.34		Gain of phosphorylation at P218 (P = 9e-04);
MVP		0.043
MPC		0.64
ClinPred		0.067	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.074
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr19-50154298;