19-49650959-C-T

Variant names:

• chr19-49650959-C-T
• rs373203311
• NM_021228.3:c.570C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_021228.3(SCAF1):​c.570C>T​(p.Pro190Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,384,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P190P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SCAF1 NM_021228.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.014).
• BP7: Synonymous conserved (PhyloP=-0.271 with no splicing effect.

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.570C>T	p.Pro190Pro	synonymous	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.570C>T	p.Pro190Pro	synonymous	Exon 7 of 11	ENSP00000353769.2	Q9H7N4
	SCAF1	ENST00000892601.1		c.591C>T	p.Pro197Pro	synonymous	Exon 6 of 10	ENSP00000562660.1
	SCAF1	ENST00000892599.1		c.570C>T	p.Pro190Pro	synonymous	Exon 7 of 11	ENSP00000562658.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1384394 Hom.: 0 Cov.: 25 AF XY: 0.00000145 AC XY: 1 AN XY: 687356

African (AFR) AF: 0.00 AC: 0 AN: 31642

American (AMR) AF: 0.00 AC: 0 AN: 40956

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23550

East Asian (EAS) AF: 0.00 AC: 0 AN: 38270

South Asian (SAS) AF: 0.00 AC: 0 AN: 78894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5554

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1058312

Other (OTH) AF: 0.00 AC: 0 AN: 57448

GnomAD4 genome Cov.: 27

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	8.2
DANN	Benign	0.76
PhyloP100		-0.27

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: rs373203311; hg19: chr19-50154216;