Variant 19-49651202-G-C 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.813G>C(p.Glu271Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00647 in 1,612,908 control chromosomes in the GnomAD database, including 42 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 3 hom., cov: 27)

Exomes 𝑓: 0.0067 ( 39 hom. )

Consequence

SCAF1
NM_021228.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0250

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=0.0045134127).

BP6

Variant 19-49651202-G-C is Benign according to our data. Variant chr19-49651202-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2650278.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SCAF1	NM_021228.3 linkuse as main transcript	c.813G>C	p.Glu271Asp	missense_variant	7/11	ENST00000360565.8	NP_067051.2
SCAF1	XM_011527194.4 linkuse as main transcript	c.822G>C	p.Glu274Asp	missense_variant	7/11		XP_011525496.1
SCAF1	XM_005259122.6 linkuse as main transcript	c.813G>C	p.Glu271Asp	missense_variant	7/11		XP_005259179.1
SCAF1	XM_017027083.3 linkuse as main transcript	c.543G>C	p.Glu181Asp	missense_variant	4/8		XP_016882572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAF1	ENST00000360565.8 linkuse as main transcript	c.813G>C	p.Glu271Asp	missense_variant	7/11	2	NM_021228.3	ENSP00000353769	P1

Frequencies

GnomAD3 genomes

AF:

0.00453

AC:

687

AN:

151666

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00788

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00714

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00368

AC:

909

AN:

247284

Hom.:

AF XY:

0.00389

AC XY:

524

AN XY:

134554

show subpopulations

Gnomad AFR exome

AF:

0.00127

Gnomad AMR exome

AF:

0.00339

Gnomad ASJ exome

AF:

0.00180

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.000417

Gnomad NFE exome

AF:

0.00656

Gnomad OTH exome

AF:

0.00312

GnomAD4 exome

AF:

0.00668

AC:

9755

AN:

1461124

Hom.:

Cov.:

AF XY:

0.00636

AC XY:

4624

AN XY:

726878

show subpopulations

Gnomad4 AFR exome

AF:

0.00138

Gnomad4 AMR exome

AF:

0.00360

Gnomad4 ASJ exome

AF:

0.00199

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.000658

Gnomad4 NFE exome

AF:

0.00811

Gnomad4 OTH exome

AF:

0.00714

GnomAD4 genome

AF:

0.00452

AC:

686

AN:

151784

Hom.:

Cov.:

AF XY:

0.00381

AC XY:

283

AN XY:

74188

show subpopulations

Gnomad4 AFR

AF:

0.00169

Gnomad4 AMR

AF:

0.00781

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00714

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00434

Hom.:

Bravo

AF:

0.00471

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00687

AC:

ExAC

AF:

0.00364

AC:

441

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

Feb 01, 2023

SCAF1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

CADD

Benign

6.9

DANN

Benign

0.40

DEOGEN2

Benign

0.029

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.44

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.0045

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.98

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.010

REVEL

Benign

0.033

Sift

Benign

0.35

Sift4G

Benign

0.66

Polyphen

0.0

Vest4

0.22

MutPred

0.13

Loss of glycosylation at P267 (P = 0.1297);

MVP

0.068

MPC

0.57

ClinPred

0.0013

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.027

gMVP

0.066

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