12-45924924-G-C

Variant names:

• chr12-45924924-G-C
• rs752583297
• NM_004719.3:c.3710C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 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
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2628417).

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.3710C>G	p.Ala1237Gly	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.3710C>G	p.Ala1237Gly	missense	Exon 12 of 15	ENSP00000358374.3	Q99590-1
	SCAF11	ENST00000549162.5	TSL:1	c.3134C>G	p.Ala1045Gly	missense	Exon 6 of 9	ENSP00000448864.1	F8VXG7
	SCAF11	ENST00000465950.5	TSL:1	c.2765C>G	p.Ala922Gly	missense	Exon 2 of 5	ENSP00000449812.1	Q99590-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250020 AF XY: 0.00

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 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

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.8	L
PhyloP100		7.5
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.15
Sift	Uncertain	0.028	D
Sift4G	Benign	0.16	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
PromoterAI		-0.025	Neutral
Varity_R		0.12
gMVP		0.25
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs752583297; hg19: chr12-46318707;