rs2081083325

Variant names:

• chr19-49651027-C-A
• NM_021228.3:c.638C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-49651027-C-A
• chr19-49651027-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_021228.3(SCAF1):​c.638C>A​(p.Pro213Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 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. P213L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 18)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: SCAF1 NM_021228.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40

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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.121961564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAF1	NM_021228.3	c.638C>A	p.Pro213Gln	missense_variant	Exon 7 of 11	ENST00000360565.8	NP_067051.2
SCAF1	XM_011527194.4	c.647C>A	p.Pro216Gln	missense_variant	Exon 7 of 11		XP_011525496.1
SCAF1	XM_005259122.6	c.638C>A	p.Pro213Gln	missense_variant	Exon 7 of 11		XP_005259179.1
SCAF1	XM_017027083.3	c.368C>A	p.Pro123Gln	missense_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.638C>A	p.Pro213Gln	missense_variant	Exon 7 of 11	2	NM_021228.3	ENSP00000353769.2
SCAF1	ENST00000598359.5	c.*29C>A		downstream_gene_variant		3		ENSP00000473210.1

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome AF: 0.00000170 AC: 1 AN: 587990 Hom.: 0 Cov.: 10 AF XY: 0.00000331 AC XY: 1 AN XY: 302380

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000359

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 18

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Benign	0.59
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.47	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.041
Sift	Benign	0.12	T
Sift4G	Benign	0.099	T
Polyphen		0.49	P
Vest4		0.34
MutPred		0.25		Loss of glycosylation at P213 (P = 4e-04);
MVP		0.082
MPC		0.59
ClinPred		0.12	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.055
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-50154284;