Variant 19-49646724-C-A 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.372C>A(p.Asp124Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SCAF1
NM_021228.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.61

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=0.0996196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAF1	NM_021228.3 link	c.372C>A	p.Asp124Glu	missense_variant	6/11	ENST00000360565.8	NP_067051.2	Q9H7N4
SCAF1	XM_011527194.4 link	c.381C>A	p.Asp127Glu	missense_variant	6/11		XP_011525496.1
SCAF1	XM_005259122.6 link	c.372C>A	p.Asp124Glu	missense_variant	6/11		XP_005259179.1	Q9H7N4
SCAF1	XM_017027083.3 link	c.102C>A	p.Asp34Glu	missense_variant	3/8		XP_016882572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAF1	ENST00000360565.8 link	c.372C>A	p.Asp124Glu	missense_variant	6/11	2	NM_021228.3	ENSP00000353769.2		Q9H7N4
SCAF1	ENST00000598359.5 link	c.372C>A	p.Asp124Glu	missense_variant	6/7	3		ENSP00000473210.1		M0R3G4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461662

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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.:

Bravo

AF:

0.00000378

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

Jul 17, 2024

The c.372C>A (p.D124E) alteration is located in exon 6 (coding exon 5) of the SCAF1 gene. This alteration results from a C to A substitution at nucleotide position 372, causing the aspartic acid (D) at amino acid position 124 to be replaced by a glutamic acid (E). 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

0.32

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.026

T;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.53

T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.95

N;.

REVEL

Benign

0.055

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.58

T;T

Polyphen

0.0060

B;.

Vest4

0.20

MutPred

0.24

Gain of glycosylation at P119 (P = 0.2038);Gain of glycosylation at P119 (P = 0.2038);

MVP

0.043

MPC

0.59

ClinPred

0.47

GERP RS

1.1

Varity_R

0.14

gMVP

0.18

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over