Variant 19-49646168-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021228.3(SCAF1):c.227G>C(p.Arg76Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,610,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SCAF1
NM_021228.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.49

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13548201).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAF1	NM_021228.3 link	c.227G>C	p.Arg76Pro	missense_variant	4/11	ENST00000360565.8	NP_067051.2	Q9H7N4
SCAF1	XM_011527194.4 link	c.236G>C	p.Arg79Pro	missense_variant	4/11		XP_011525496.1
SCAF1	XM_005259122.6 link	c.227G>C	p.Arg76Pro	missense_variant	4/11		XP_005259179.1	Q9H7N4
SCAF1	XM_017027083.3 link	c.-76G>C		5_prime_UTR_variant	1/8		XP_016882572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SCAF1	ENST00000360565.8 link	c.227G>C	p.Arg76Pro	missense_variant	4/11	2	NM_021228.3	ENSP00000353769.2	Q9H7N4
SCAF1	ENST00000598359.5 link	c.227G>C	p.Arg76Pro	missense_variant	4/7	3		ENSP00000473210.1	M0R3G4
SCAF1	ENST00000595242.3 link	c.227G>C	p.Arg76Pro	missense_variant	3/4	3		ENSP00000472276.1	M0R232
SCAF1	ENST00000601038.5 link	c.227G>C	p.Arg76Pro	missense_variant	3/4	3		ENSP00000472649.1	M0R2L3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151840

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248680

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134638

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1458804

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725814

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151840

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74118

show subpopulations

Gnomad4 AFR

AF:

0.0000968

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

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

Sep 30, 2024

The c.227G>C (p.R76P) alteration is located in exon 4 (coding exon 3) of the SCAF1 gene. This alteration results from a G to C substitution at nucleotide position 227, causing the arginine (R) at amino acid position 76 to be replaced by a proline (P). 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

0.13

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.042

T;T;T;.

Eigen

Benign

0.032

Eigen_PC

Benign

0.032

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.68

T;T;T;T

M_CAP

Benign

0.071

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;.;.;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.3

N;.;.;.

REVEL

Benign

0.12

Sift

Uncertain

0.0040

D;.;.;.

Sift4G

Benign

0.32

T;T;D;D

Polyphen

0.97

D;.;.;.

Vest4

0.47

MVP

0.56

MPC

0.91

ClinPred

0.21

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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