chr19-49650907-G-T

Variant names:

• chr19-49650907-G-T
• rs138080693
• NM_021228.3:c.518G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021228.3(SCAF1):​c.518G>T​(p.Arg173Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R173P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCAF1 NM_021228.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.748
• Publications: 0 publications found

Genes affected

SCAF1 (HGNC:30403): (SR-related CTD associated factor 1) Enables RNA polymerase II C-terminal domain binding activity. Predicted to be involved in RNA splicing; mRNA processing; and transcription by RNA polymerase II. Predicted to be located in nucleus. [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=0.14637172).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021228.3. 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
	SCAF1	NM_021228.3	MANE Select	c.518G>T	p.Arg173Leu	missense	Exon 7 of 11	NP_067051.2	Q9H7N4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAF1	ENST00000360565.8	TSL:2 MANE Select	c.518G>T	p.Arg173Leu	missense	Exon 7 of 11	ENSP00000353769.2	Q9H7N4
	SCAF1	ENST00000892601.1		c.539G>T	p.Arg180Leu	missense	Exon 6 of 10	ENSP00000562660.1
	SCAF1	ENST00000892599.1		c.518G>T	p.Arg173Leu	missense	Exon 7 of 11	ENSP00000562658.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.75
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.061
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.61	T
Polyphen		0.49	P
Vest4		0.39
MutPred		0.32		Gain of sheet (P = 0.0344)
MVP		0.043
MPC		0.79
ClinPred		0.41	T
GERP RS		3.4
Varity_R		0.19
gMVP		0.28
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs138080693; hg19: chr19-50154164;