19-49645354-C-G

Position:

chr19-49645354-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_021228.3(SCAF1):c.109C>G(p.Arg37Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000165 in 1,613,790 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 5 hom. )

Consequence

SCAF1
NM_021228.3 missense, splice_region

Scores

Splicing: ADA: 0.001766

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13560688).

BS2

High Homozygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SCAF1	NM_021228.3 linkuse as main transcript	c.109C>G	p.Arg37Gly	missense_variant, splice_region_variant	3/11	ENST00000360565.8	NP_067051.2
SCAF1	XM_011527194.4 linkuse as main transcript	c.118C>G	p.Arg40Gly	missense_variant, splice_region_variant	3/11		XP_011525496.1
SCAF1	XM_005259122.6 linkuse as main transcript	c.109C>G	p.Arg37Gly	missense_variant, splice_region_variant	3/11		XP_005259179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SCAF1	ENST00000360565.8 linkuse as main transcript	c.109C>G	p.Arg37Gly	missense_variant, splice_region_variant	3/11	2	NM_021228.3	ENSP00000353769	P1
SCAF1	ENST00000598359.5 linkuse as main transcript	c.109C>G	p.Arg37Gly	missense_variant, splice_region_variant	3/7	3		ENSP00000473210
SCAF1	ENST00000595242.3 linkuse as main transcript	c.109C>G	p.Arg37Gly	missense_variant, splice_region_variant	2/4	3		ENSP00000472276
SCAF1	ENST00000601038.5 linkuse as main transcript	c.109C>G	p.Arg37Gly	missense_variant, splice_region_variant	2/4	3		ENSP00000472649

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

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:

0.000103

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000207

AC:

AN:

251040

Hom.:

AF XY:

0.000228

AC XY:

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000406

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000882

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000792

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000169

AC:

247

AN:

1461562

Hom.:

Cov.:

AF XY:

0.000186

AC XY:

135

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000730

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000136

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000125

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.000219

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000189

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

Aug 08, 2023

The c.109C>G (p.R37G) alteration is located in exon 3 (coding exon 2) of the SCAF1 gene. This alteration results from a C to G substitution at nucleotide position 109, causing the arginine (R) at amino acid position 37 to be replaced by a glycine (G). 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

Pathogenic

0.58

BayesDel_addAF

Uncertain

0.076

BayesDel_noAF

Pathogenic

0.26

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.066

T;T;T;.

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.72

T;T;T;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.55

N;.;.;.

MutationTaster

Benign

0.66

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.6

N;.;.;.

REVEL

Benign

0.24

Sift

Pathogenic

0.0

D;.;.;.

Sift4G

Uncertain

0.0080

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.80

MutPred

0.28

Gain of catalytic residue at A38 (P = 0.1007);Gain of catalytic residue at A38 (P = 0.1007);Gain of catalytic residue at A38 (P = 0.1007);Gain of catalytic residue at A38 (P = 0.1007);

MVP

0.78

MPC

0.81

ClinPred

0.090

GERP RS

4.1

Varity_R

0.35

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0018

dbscSNV1_RF

Benign

0.15

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