chr19-49651033-C-A

Variant names:

• chr19-49651033-C-A
• rs1368888363
• NM_021228.3:c.644C>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>A​(p.Pro215His) 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. 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. P215L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 17)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: SCAF1 NM_021228.3 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.17235851).

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>A	p.Pro215His	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>A	p.Pro215His	missense	Exon 7 of 11	ENSP00000353769.2	Q9H7N4
	SCAF1	ENST00000892601.1		c.665C>A	p.Pro222His	missense	Exon 6 of 10	ENSP00000562660.1
	SCAF1	ENST00000892599.1		c.644C>A	p.Pro215His	missense	Exon 7 of 11	ENSP00000562658.1

Frequencies

GnomAD3 genomes Cov.: 17

GnomAD4 exome AF: 0.00000156 AC: 1 AN: 640218 Hom.: 0 Cov.: 11 AF XY: 0.00000306 AC XY: 1 AN XY: 326974

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 0.0000190 AC: 1 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: 0.00 AC: 0 AN: 445308

Other (OTH) AF: 0.00 AC: 0 AN: 31522

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 17

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Benign	0.72
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.40	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.8
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.074
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.092	T
Polyphen		0.97	D
Vest4		0.35
MutPred		0.28		Loss of glycosylation at P215 (P = 7e-04)
MVP		0.043
MPC		0.73
ClinPred		0.30	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.20
Mutation Taster		=92/8	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: rs1368888363; hg19: chr19-50154290;