Variant 19-49645079-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.53G>A(p.Arg18Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000432 in 1,614,150 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 2 hom. )

Consequence

SCAF1
NM_021228.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.06

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=0.0051369667).

BP6

Variant 19-49645079-G-A is Benign according to our data. Variant chr19-49645079-G-A is described in ClinVar as [Benign]. Clinvar id is 710861.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SCAF1	NM_021228.3 linkuse as main transcript	c.53G>A	p.Arg18Gln	missense_variant	2/11	ENST00000360565.8
SCAF1	XM_011527194.4 linkuse as main transcript	c.62G>A	p.Arg21Gln	missense_variant	2/11
SCAF1	XM_005259122.6 linkuse as main transcript	c.53G>A	p.Arg18Gln	missense_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SCAF1	ENST00000360565.8 linkuse as main transcript	c.53G>A	p.Arg18Gln	missense_variant	2/11	2	NM_021228.3	P1
SCAF1	ENST00000598359.5 linkuse as main transcript	c.53G>A	p.Arg18Gln	missense_variant	2/7	3
SCAF1	ENST00000595242.3 linkuse as main transcript	c.53G>A	p.Arg18Gln	missense_variant	1/4	3
SCAF1	ENST00000601038.5 linkuse as main transcript	c.53G>A	p.Arg18Gln	missense_variant	1/4	3

Frequencies

GnomAD3 genomes

AF:

0.00251

AC:

382

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00874

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000785

AC:

197

AN:

251066

Hom.:

AF XY:

0.000589

AC XY:

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.0100

Gnomad AMR exome

AF:

0.000868

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000215

AC:

315

AN:

1461838

Hom.:

Cov.:

AF XY:

0.000212

AC XY:

154

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00663

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.00251

AC:

382

AN:

152312

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

172

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00871

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000894

Hom.:

Bravo

AF:

0.00274

ESP6500AA

AF:

0.0113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000980

AC:

119

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.24

Cadd

Uncertain

Dann

Benign

0.95

DEOGEN2

Benign

0.048

T;T;T;.

Eigen

Benign

0.032

Eigen_PC

Benign

-0.034

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.70

T;T;T;T

MetaRNN

Benign

0.0051

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.;.;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.3

N;.;.;.

REVEL

Benign

0.093

Sift

Pathogenic

0.0

D;.;.;.

Sift4G

Uncertain

0.048

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.45

MVP

0.42

MPC

0.73

ClinPred

0.082

GERP RS

2.9

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.0

Varity_R

0.13

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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