dbSNP rs138080693: SCAF1:p.Arg173His (chr19-49650907-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021228.3(SCAF1):c.518G>A(p.Arg173His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,610,160 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R173P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

SCAF1
NM_021228.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.748

Variant links:

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]

SCAF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.114783674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAF1	NM_021228.3 link	c.518G>A	p.Arg173His	missense_variant	Exon 7 of 11	ENST00000360565.8	NP_067051.2	Q9H7N4
SCAF1	XM_011527194.4 link	c.527G>A	p.Arg176His	missense_variant	Exon 7 of 11		XP_011525496.1
SCAF1	XM_005259122.6 link	c.518G>A	p.Arg173His	missense_variant	Exon 7 of 11		XP_005259179.1	Q9H7N4
SCAF1	XM_017027083.3 link	c.248G>A	p.Arg83His	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 link	c.518G>A	p.Arg173His	missense_variant	Exon 7 of 11	2	NM_021228.3	ENSP00000353769.2		Q9H7N4
SCAF1	ENST00000598359.5 link	c.518G>A	p.Arg173His	missense_variant	Exon 7 of 7	3		ENSP00000473210.1		M0R3G4

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000166

AC:

AN:

241464

Hom.:

AF XY:

0.0000152

AC XY:

AN XY:

131486

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000375

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1458232

Hom.:

Cov.:

AF XY:

0.0000207

AC XY:

AN XY:

725242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000451

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151928

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000568

Hom.:

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.045

T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.044

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.031

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.37

T;D

Polyphen

0.0070

B;.

Vest4

0.15

MutPred

0.31

Gain of catalytic residue at L175 (P = 0.0485);Gain of catalytic residue at L175 (P = 0.0485);

MVP

0.043

MPC

0.79

ClinPred

0.26

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.10

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over