Variant 19-49651054-C-T 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.665C>T(p.Ala222Val) 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: 𝑓 0.00012 ( 0 hom., cov: 18)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

SCAF1
NM_021228.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14

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=0.031513393).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SCAF1	NM_021228.3 linkuse as main transcript	c.665C>T	p.Ala222Val	missense_variant	7/11	ENST00000360565.8	NP_067051.2
SCAF1	XM_011527194.4 linkuse as main transcript	c.674C>T	p.Ala225Val	missense_variant	7/11		XP_011525496.1
SCAF1	XM_005259122.6 linkuse as main transcript	c.665C>T	p.Ala222Val	missense_variant	7/11		XP_005259179.1
SCAF1	XM_017027083.3 linkuse as main transcript	c.395C>T	p.Ala132Val	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.665C>T	p.Ala222Val	missense_variant	7/11	2	NM_021228.3	ENSP00000353769	P1

Frequencies

GnomAD3 genomes

AF:

0.000122

AC:

AN:

139892

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000535

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000212

Gnomad ASJ

AF:

0.000907

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000141

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000195

AC:

AN:

174682

Hom.:

AF XY:

0.000221

AC XY:

AN XY:

95026

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000284

Gnomad ASJ exome

AF:

0.000609

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000299

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000187

AC:

243

AN:

1302768

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

131

AN XY:

640706

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000222

Gnomad4 ASJ exome

AF:

0.000292

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000223

Gnomad4 OTH exome

AF:

0.0000739

GnomAD4 genome

AF:

0.000121

AC:

AN:

139986

Hom.:

Cov.:

AF XY:

0.0000737

AC XY:

AN XY:

67854

show subpopulations

Gnomad4 AFR

AF:

0.0000534

Gnomad4 AMR

AF:

0.000212

Gnomad4 ASJ

AF:

0.000907

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000141

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000147

Hom.:

ExAC

AF:

0.000157

AC:

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

May 24, 2023

The c.665C>T (p.A222V) 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 665, causing the alanine (A) at amino acid position 222 to be replaced by a valine (V). 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

0.20

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.047

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.54

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.032

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.0

REVEL

Benign

0.021

Sift

Uncertain

0.0020

Sift4G

Benign

0.12

Polyphen

0.017

Vest4

0.19

MVP

0.043

MPC

0.63

ClinPred

0.051

GERP RS

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.23

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