12-45926157-C-T

Variant names:

• chr12-45926157-C-T
• NM_004719.3:c.3544G>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_004719.3(SCAF11):​c.3544G>A​(p.Glu1182Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,459,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SCAF11 NM_004719.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.55

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18852228).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAF11	NM_004719.3	c.3544G>A	p.Glu1182Lys	missense_variant	Exon 11 of 15	ENST00000369367.8	NP_004710.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAF11	ENST00000369367.8	c.3544G>A	p.Glu1182Lys	missense_variant	Exon 11 of 15	1	NM_004719.3	ENSP00000358374.3
SCAF11	ENST00000549162.5	c.2968G>A	p.Glu990Lys	missense_variant	Exon 5 of 9	1		ENSP00000448864.1
SCAF11	ENST00000465950.5	c.2599G>A	p.Glu867Lys	missense_variant	Exon 1 of 5	1		ENSP00000449812.1
SCAF11	ENST00000547950.1	n.554G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1459102 Hom.: 0 Cov.: 32 AF XY: 0.00000551 AC XY: 4 AN XY: 725374

Gnomad4 AFR exome AF: 0.00

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: 0.00000360

Gnomad4 OTH exome AF: 0.0000332

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3544G>A (p.E1182K) alteration is located in exon 11 (coding exon 10) of the SCAF11 gene. This alteration results from a G to A substitution at nucleotide position 3544, causing the glutamic acid (E) at amino acid position 1182 to be replaced by a lysine (K). 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	0.23
BayesDel_addAF	Benign	-0.0094	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	2.0	M;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.22
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.049	D;T;T
Polyphen		1.0	D;.;P
Vest4		0.48
MutPred		0.28		Gain of methylation at E1182 (P = 0.0036);.;.;
MVP		0.19
MPC		0.26
ClinPred		0.92	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.13
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-46319940;