Variant 19-49646156-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_021228.3(SCAF1):c.215G>T(p.Arg72Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SCAF1
NM_021228.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.09

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:

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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=0.15095276).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAF1	NM_021228.3 link	c.215G>T	p.Arg72Leu	missense_variant	4/11	ENST00000360565.8	NP_067051.2	Q9H7N4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SCAF1	ENST00000360565.8 link	c.215G>T	p.Arg72Leu	missense_variant	4/11	2	NM_021228.3	ENSP00000353769.2	Q9H7N4
SCAF1	ENST00000598359.5 link	c.215G>T	p.Arg72Leu	missense_variant	4/7	3		ENSP00000473210.1	M0R3G4
SCAF1	ENST00000595242.3 link	c.215G>T	p.Arg72Leu	missense_variant	3/4	3		ENSP00000472276.1	M0R232
SCAF1	ENST00000601038.5 link	c.215G>T	p.Arg72Leu	missense_variant	3/4	3		ENSP00000472649.1	M0R2L3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1459398

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726074

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2024

The c.215G>T (p.R72L) alteration is located in exon 4 (coding exon 3) of the SCAF1 gene. This alteration results from a G to T substitution at nucleotide position 215, causing the arginine (R) at amino acid position 72 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.059

T;T;T;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.093

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.76

T;T;T;T

M_CAP

Benign

0.081

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;.;.;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.4

N;.;.;.

REVEL

Benign

0.17

Sift

Pathogenic

0.0

D;.;.;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.67

P;.;.;.

Vest4

0.53

MutPred

0.30

Loss of solvent accessibility (P = 0.0013);Loss of solvent accessibility (P = 0.0013);Loss of solvent accessibility (P = 0.0013);Loss of solvent accessibility (P = 0.0013);

MVP

0.34

MPC

0.79

ClinPred

0.58

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over