chr12-45926500-C-A

Position:

• chr12-45926500-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004719.3(SCAF11):​c.3201G>T​(p.Trp1067Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCAF11 NM_004719.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.22

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCAF11	NM_004719.3	c.3201G>T	p.Trp1067Cys	missense_variant	11/15	ENST00000369367.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCAF11	ENST00000369367.8	c.3201G>T	p.Trp1067Cys	missense_variant	11/15	1	NM_004719.3	P1
SCAF11	ENST00000549162.5	c.2625G>T	p.Trp875Cys	missense_variant	5/9	1
SCAF11	ENST00000465950.5	c.2256G>T	p.Trp752Cys	missense_variant	1/5	1
SCAF11	ENST00000547950.1	n.211G>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2023

The c.3201G>T (p.W1067C) 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 3201, causing the tryptophan (W) at amino acid position 1067 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	0.78
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T;.;T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-0.28	T
MutationAssessor	Uncertain	2.1	M;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-4.4	D;D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.011	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.54
MutPred		0.32		Gain of catalytic residue at G1072 (P = 0.0155);.;.;
MVP		0.30
MPC		0.33
ClinPred		1.0	D
GERP RS		5.9
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.34
gMVP		0.24

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: chr12-46320283;