Variant 19-49650933-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021228.3(SCAF1):c.544G>A(p.Gly182Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00469 in 1,601,678 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 24 hom. )

Consequence

SCAF1
NM_021228.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.24

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059126616).

BP6

Variant 19-49650933-G-A is Benign according to our data. Variant chr19-49650933-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2650275.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SCAF1	NM_021228.3 linkuse as main transcript	c.544G>A	p.Gly182Arg	missense_variant	7/11	ENST00000360565.8
SCAF1	XM_011527194.4 linkuse as main transcript	c.553G>A	p.Gly185Arg	missense_variant	7/11
SCAF1	XM_005259122.6 linkuse as main transcript	c.544G>A	p.Gly182Arg	missense_variant	7/11
SCAF1	XM_017027083.3 linkuse as main transcript	c.274G>A	p.Gly92Arg	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCAF1	ENST00000360565.8 linkuse as main transcript	c.544G>A	p.Gly182Arg	missense_variant	7/11	2	NM_021228.3	P1
SCAF1	ENST00000598359.5 linkuse as main transcript	c.544G>A	p.Gly182Arg	missense_variant	7/7	3

Frequencies

GnomAD3 genomes

AF:

0.00378

AC:

574

AN:

151696

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000945

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00472

Gnomad ASJ

AF:

0.00953

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000624

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00593

Gnomad OTH

AF:

0.00817

GnomAD3 exomes

AF:

0.00377

AC:

872

AN:

231020

Hom.:

AF XY:

0.00365

AC XY:

460

AN XY:

125882

show subpopulations

Gnomad AFR exome

AF:

0.000728

Gnomad AMR exome

AF:

0.00425

Gnomad ASJ exome

AF:

0.00780

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000565

Gnomad FIN exome

AF:

0.000245

Gnomad NFE exome

AF:

0.00580

Gnomad OTH exome

AF:

0.00709

GnomAD4 exome

AF:

0.00478

AC:

6935

AN:

1449864

Hom.:

Cov.:

AF XY:

0.00471

AC XY:

3392

AN XY:

720672

show subpopulations

Gnomad4 AFR exome

AF:

0.000691

Gnomad4 AMR exome

AF:

0.00462

Gnomad4 ASJ exome

AF:

0.00823

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000437

Gnomad4 FIN exome

AF:

0.000479

Gnomad4 NFE exome

AF:

0.00551

Gnomad4 OTH exome

AF:

0.00527

GnomAD4 genome

AF:

0.00377

AC:

572

AN:

151814

Hom.:

Cov.:

AF XY:

0.00322

AC XY:

239

AN XY:

74188

show subpopulations

Gnomad4 AFR

AF:

0.000942

Gnomad4 AMR

AF:

0.00472

Gnomad4 ASJ

AF:

0.00953

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000625

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00591

Gnomad4 OTH

AF:

0.00809

Alfa

AF:

0.00541

Hom.:

Bravo

AF:

0.00430

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00558

AC:

ExAC

AF:

0.00344

AC:

416

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

SCAF1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.34

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.056

T;T

Eigen

Benign

0.029

Eigen_PC

Benign

0.095

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.59

T;T

MetaRNN

Benign

0.0059

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.90

L;.

MutationTaster

Benign

0.72

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-2.0

N;.

REVEL

Benign

0.071

Sift

Uncertain

0.0020

D;.

Sift4G

Uncertain

0.026

D;D

Polyphen

0.78

P;.

Vest4

0.45

MutPred

0.077

Gain of solvent accessibility (P = 0.019);Gain of solvent accessibility (P = 0.019);

MVP

0.093

MPC

0.76

ClinPred

0.019

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.060

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

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