12-45924914-C-T

Variant names:

• chr12-45924914-C-T
• rs146401933
• NM_004719.3:c.3720G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004719.3(SCAF11):​c.3720G>A​(p.Met1240Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCAF11 NM_004719.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.05
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3364358).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004719.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAF11	NM_004719.3	MANE Select	c.3720G>A	p.Met1240Ile	missense	Exon 12 of 15	NP_004710.2	Q99590-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAF11	ENST00000369367.8	TSL:1 MANE Select	c.3720G>A	p.Met1240Ile	missense	Exon 12 of 15	ENSP00000358374.3	Q99590-1
	SCAF11	ENST00000549162.5	TSL:1	c.3144G>A	p.Met1048Ile	missense	Exon 6 of 9	ENSP00000448864.1	F8VXG7
	SCAF11	ENST00000465950.5	TSL:1	c.2775G>A	p.Met925Ile	missense	Exon 2 of 5	ENSP00000449812.1	Q99590-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.0
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.078
Sift	Benign	0.037	D
Sift4G	Benign	0.12	T
Polyphen		0.85	P
Vest4		0.51
MutPred		0.37		Gain of catalytic residue at V1235 (P = 0)
MVP		0.22
MPC		0.050
ClinPred		0.81	D
GERP RS		5.1
PromoterAI		-0.0081	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.15
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs146401933; hg19: chr12-46318697;