19-49650959-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_021228.3(SCAF1):​c.570C>G​(p.Pro190Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 151,100 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: 𝑓 0.0000066 (0 hom., cov: 27)
• Consequence: SCAF1 NM_021228.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271

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

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=-0.271 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAF1	NM_021228.3	c.570C>G	p.Pro190Pro	synonymous_variant	Exon 7 of 11	ENST00000360565.8	NP_067051.2
SCAF1	XM_011527194.4	c.579C>G	p.Pro193Pro	synonymous_variant	Exon 7 of 11		XP_011525496.1
SCAF1	XM_005259122.6	c.570C>G	p.Pro190Pro	synonymous_variant	Exon 7 of 11		XP_005259179.1
SCAF1	XM_017027083.3	c.300C>G	p.Pro100Pro	synonymous_variant	Exon 4 of 8		XP_016882572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAF1	ENST00000360565.8	c.570C>G	p.Pro190Pro	synonymous_variant	Exon 7 of 11	2	NM_021228.3	ENSP00000353769.2
SCAF1	ENST00000598359.5	c.570C>G	p.Pro190Pro	synonymous_variant	Exon 7 of 7	3		ENSP00000473210.1

Frequencies

GnomAD3 genomes AF: 0.00000662 AC: 1 AN: 151100 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 25

GnomAD4 genome AF: 0.00000662 AC: 1 AN: 151100 Hom.: 0 Cov.: 27 AF XY: 0.0000136 AC XY: 1 AN XY: 73770

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.5
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs373203311; hg19: chr19-50154216;