12-45924924-G-C

Position:

• chr12-45924924-G-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.3710C>G​(p.Ala1237Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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)
• Consequence: SCAF11 NM_004719.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.51

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=0.2628417).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCAF11	NM_004719.3	c.3710C>G	p.Ala1237Gly	missense_variant	12/15	ENST00000369367.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCAF11	ENST00000369367.8	c.3710C>G	p.Ala1237Gly	missense_variant	12/15	1	NM_004719.3	P1
SCAF11	ENST00000549162.5	c.3134C>G	p.Ala1045Gly	missense_variant	6/9	1
SCAF11	ENST00000465950.5	c.2765C>G	p.Ala922Gly	missense_variant	2/5	1
SCAF11	ENST00000547950.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250020 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135300

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

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 Cov.: 34

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

Jan 30, 2024

The c.3710C>G (p.A1237G) 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 3710, causing the alanine (A) at amino acid position 1237 to be replaced by a glycine (G). 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	0.24
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T;.;T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.8	L;.;.
MutationTaster	Benign	0.98	N;N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.98	N;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.028	D;D;D
Sift4G	Benign	0.16	T;T;T
Polyphen		0.99	D;.;.
Vest4		0.25
MutPred		0.35		Gain of catalytic residue at A1237 (P = 0);.;.;
MVP		0.32
MPC		0.26
ClinPred		0.74	D
GERP RS		5.1
Varity_R		0.12
gMVP		0.25

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

LitVar

Other links and lift over

dbSNP: rs752583297; hg19: chr12-46318707;