12-45925071-G-C

Variant names:

• chr12-45925071-G-C
• rs779566035
• NM_004719.3:c.3563C>G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004719.3(SCAF11):​c.3563C>G​(p.Ser1188Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000555 in 1,442,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: SCAF11 NM_004719.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.78

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.045810997).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAF11	NM_004719.3	c.3563C>G	p.Ser1188Cys	missense_variant	Exon 12 of 15	ENST00000369367.8	NP_004710.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAF11	ENST00000369367.8	c.3563C>G	p.Ser1188Cys	missense_variant	Exon 12 of 15	1	NM_004719.3	ENSP00000358374.3
SCAF11	ENST00000549162.5	c.2987C>G	p.Ser996Cys	missense_variant	Exon 6 of 9	1		ENSP00000448864.1
SCAF11	ENST00000465950.5	c.2618C>G	p.Ser873Cys	missense_variant	Exon 2 of 5	1		ENSP00000449812.1
SCAF11	ENST00000547950.1	n.573C>G		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000209 AC: 5 AN: 239702 Hom.: 0 AF XY: 0.0000153 AC XY: 2 AN XY: 130316

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000280

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: 0.00000555 AC: 8 AN: 1442680 Hom.: 0 Cov.: 33 AF XY: 0.00000140 AC XY: 1 AN XY: 715496

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000204

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 Cov.: 32

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3563C>G (p.S1188C) alteration is located in exon 12 (coding exon 11) of the SCAF11 gene. This alteration results from a C to G substitution at nucleotide position 3563, causing the serine (S) at amino acid position 1188 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	Benign	0.097
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Benign	0.91
DEOGEN2	Benign	0.027	T;.;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.051
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.046	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.0	L;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.050
Sift	Benign	0.11	T;T;T
Sift4G	Uncertain	0.055	T;T;T
Polyphen		0.016	B;.;.
Vest4		0.13
MutPred		0.21		Loss of phosphorylation at S1188 (P = 0.0249);.;.;
MVP		0.10
MPC		0.040
ClinPred		0.13	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.074
gMVP		0.17

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

Other links and lift over

dbSNP: rs779566035; hg19: chr12-46318854;