rs1368888363

Variant names:

• chr19-49651033-C-T
• rs1368888363
• NM_021228.3:c.644C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-49651033-C-T
• chr19-49651033-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_021228.3(SCAF1):​c.644C>T​(p.Pro215Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000022 (0 hom., cov: 17)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SCAF1 NM_021228.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.82
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07001847).

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.644C>T	p.Pro215Leu	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.644C>T	p.Pro215Leu	missense	Exon 7 of 11	ENSP00000353769.2	Q9H7N4
	SCAF1	ENST00000892601.1		c.665C>T	p.Pro222Leu	missense	Exon 6 of 10	ENSP00000562660.1
	SCAF1	ENST00000892599.1		c.644C>T	p.Pro215Leu	missense	Exon 7 of 11	ENSP00000562658.1

Frequencies

GnomAD3 genomes AF: 0.0000218 AC: 3 AN: 137868 Hom.: 0 Cov.: 17

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: 0.0000478

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000141 AC: 9 AN: 640218 Hom.: 0 Cov.: 11 AF XY: 0.00000612 AC XY: 2 AN XY: 326974

African (AFR) AF: 0.00 AC: 0 AN: 15350

American (AMR) AF: 0.00 AC: 0 AN: 21262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14466

East Asian (EAS) AF: 0.00 AC: 0 AN: 28106

South Asian (SAS) AF: 0.00 AC: 0 AN: 52686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2280

European-Non Finnish (NFE) AF: 0.0000180 AC: 8 AN: 445308

Other (OTH) AF: 0.0000317 AC: 1 AN: 31522

GnomAD4 genome AF: 0.0000218 AC: 3 AN: 137868 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 66604

African (AFR) AF: 0.00 AC: 0 AN: 37062

American (AMR) AF: 0.00 AC: 0 AN: 13896

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3278

East Asian (EAS) AF: 0.00 AC: 0 AN: 4494

South Asian (SAS) AF: 0.00 AC: 0 AN: 4024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.0000478 AC: 3 AN: 62714

Other (OTH) AF: 0.00 AC: 0 AN: 1828

Alfa AF: 0.00 Hom.: 0

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	0.14
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Benign	0.65
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.53	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.8
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.036
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.13	T
Polyphen		0.0	B
Vest4		0.28
MutPred		0.31		Loss of glycosylation at P215 (P = 7e-04)
MVP		0.043
MPC		0.65
ClinPred		0.21	T
GERP RS		3.0
Varity_R		0.075
gMVP		0.20
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1368888363; hg19: chr19-50154290;