12-45922062-T-C

Position:

• chr12-45922062-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004719.3(SCAF11):​c.4378A>G​(p.Lys1460Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 6.9e-7 (0 hom.)
• Consequence: SCAF11 NM_004719.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.82

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10786888).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCAF11	NM_004719.3	c.4378A>G	p.Lys1460Glu	missense_variant	15/15	ENST00000369367.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCAF11	ENST00000369367.8	c.4378A>G	p.Lys1460Glu	missense_variant	15/15	1	NM_004719.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459176 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725880

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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

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 16, 2023

The c.4378A>G (p.K1460E) alteration is located in exon 15 (coding exon 14) of the SCAF11 gene. This alteration results from a A to G substitution at nucleotide position 4378, causing the lysine (K) at amino acid position 1460 to be replaced by a glutamic acid (E). 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	0.16
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T;.;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.029
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.64	T;T;T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N;.;.
MutationTaster	Benign	0.95	N;N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.057
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		0.068	B;.;.
Vest4		0.24
MutPred		0.21		Loss of ubiquitination at K1460 (P = 6e-04);.;.;
MVP		0.19
MPC		1.6
ClinPred		0.80	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.28
gMVP		0.088

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: chr12-46315845;