Genetic Variant SCAF11:p.Trp1047Cys (chr12-45926560-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004719.3(SCAF11):c.3141G>T(p.Trp1047Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,612,234 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W1047L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SCAF11
NM_004719.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.97

Variant links:

Genes affected

SCAF11 (HGNC:10784): (SR-related CTD associated factor 11) Enables RNA binding activity. Involved in spliceosomal complex assembly. Located in nuclear body and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

SCAF11 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAF11	NM_004719.3 link	c.3141G>T	p.Trp1047Cys	missense_variant	Exon 11 of 15	ENST00000369367.8	NP_004710.2	Q99590-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAF11	ENST00000369367.8 link	c.3141G>T	p.Trp1047Cys	missense_variant	Exon 11 of 15	1	NM_004719.3	ENSP00000358374.3		Q99590-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460088

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726368

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

33202

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

44280

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26102

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39688

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

85740

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53400

Gnomad4 NFE exome

AF:

9.00e-7

AC:

AN:

1111638

Gnomad4 Remaining exome

AF:

0.00

AC:

AN:

60280

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.00

AC:

AN:

Gnomad4 AMR

AF:

0.0000654

AC:

0.000065445

AN:

0.000065445

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.00

AC:

AN:

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 09, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.3141G>T (p.W1047C) alteration is located in exon 11 (coding exon 10) of the SCAF11 gene. This alteration results from a G to T substitution at nucleotide position 3141, causing the tryptophan (W) at amino acid position 1047 to be replaced by a cysteine (C). 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

0.76

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

T;.;T

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.56

D;D;D

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.5

M;.;.

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-4.5

D;D;D

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.019

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.86

MutPred

0.24

Gain of catalytic residue at L1042 (P = 0.0672);.;.;

MVP

0.18

MPC

0.33

ClinPred

1.0

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.47

gMVP

0.26

Mutation Taster

=65/35

polymorphism

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