NM_021228.3:c.491C>G

Variant names:

• chr19-49650880-C-G
• rs747053810
• NM_021228.3:c.491C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021228.3(SCAF1):​c.491C>G​(p.Ser164Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,457,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. S164L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SCAF1 NM_021228.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16905305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAF1	NM_021228.3	c.491C>G	p.Ser164Trp	missense_variant	Exon 7 of 11	ENST00000360565.8	NP_067051.2
SCAF1	XM_011527194.4	c.500C>G	p.Ser167Trp	missense_variant	Exon 7 of 11		XP_011525496.1
SCAF1	XM_005259122.6	c.491C>G	p.Ser164Trp	missense_variant	Exon 7 of 11		XP_005259179.1
SCAF1	XM_017027083.3	c.221C>G	p.Ser74Trp	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.491C>G	p.Ser164Trp	missense_variant	Exon 7 of 11	2	NM_021228.3	ENSP00000353769.2
SCAF1	ENST00000598359.5	c.491C>G	p.Ser164Trp	missense_variant	Exon 7 of 7	3		ENSP00000473210.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000830 AC: 2 AN: 241098 Hom.: 0 AF XY: 0.0000152 AC XY: 2 AN XY: 131154

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000589

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1457548 Hom.: 0 Cov.: 31 AF XY: 0.00000552 AC XY: 4 AN XY: 724898

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000452

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.17	T;T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.7	D;.
REVEL	Benign	0.17
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.011	D;D
Polyphen		0.97	D;.
Vest4		0.41
MutPred		0.20		Loss of glycosylation at S164 (P = 0.0057);Loss of glycosylation at S164 (P = 0.0057);
MVP		0.082
MPC		0.87
ClinPred		0.81	D
GERP RS		4.4
Varity_R		0.15
gMVP		0.31

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: rs747053810; hg19: chr19-50154137;