Variant 19-49651041-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021228.3(SCAF1):c.652C>G(p.Pro218Ala) 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: 0.000023 ( 0 hom. )

Consequence

SCAF1
NM_021228.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.549

Variant links:

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]

SCAF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0563145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAF1	NM_021228.3 link	c.652C>G	p.Pro218Ala	missense_variant	7/11	ENST00000360565.8	NP_067051.2	Q9H7N4
SCAF1	XM_011527194.4 link	c.661C>G	p.Pro221Ala	missense_variant	7/11		XP_011525496.1
SCAF1	XM_005259122.6 link	c.652C>G	p.Pro218Ala	missense_variant	7/11		XP_005259179.1	Q9H7N4
SCAF1	XM_017027083.3 link	c.382C>G	p.Pro128Ala	missense_variant	4/8		XP_016882572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAF1	ENST00000360565.8 link	c.652C>G	p.Pro218Ala	missense_variant	7/11	2	NM_021228.3	ENSP00000353769.2		Q9H7N4
SCAF1	ENST00000598359.5 link	c.*43C>G		downstream_gene_variant		3		ENSP00000473210.1		M0R3G4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000549

AC:

AN:

91156

Hom.:

AF XY:

0.000105

AC XY:

AN XY:

47628

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000436

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000230

AC:

AN:

869904

Hom.:

Cov.:

AF XY:

0.0000253

AC XY:

AN XY:

434074

show subpopulations

Gnomad4 AFR exome

AF:

0.0000505

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000257

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000104

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 24, 2024

The c.652C>G (p.P218A) alteration is located in exon 7 (coding exon 6) of the SCAF1 gene. This alteration results from a C to G substitution at nucleotide position 652, causing the proline (P) at amino acid position 218 to be replaced by an alanine (A). 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

0.069

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.47

DEOGEN2

Benign

0.053

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.49

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.056

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.0

REVEL

Benign

0.041

Sift

Uncertain

0.014

Sift4G

Benign

0.092

Polyphen

0.0030

Vest4

0.21

MutPred

0.15

Loss of glycosylation at P218 (P = 0.003);

MVP

0.068

MPC

0.62

ClinPred

0.025

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.090

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over