Variant 21-31671714-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020706.2(SCAF4):c.3129C>G(p.His1043Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SCAF4
NM_020706.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30

Variant links:

Genes affected

SCAF4 (HGNC:19304): (SR-related CTD associated factor 4) This gene likely encodes a member of the arginine/serine-rich splicing factor family. A similar protein in Rat appears to bind the large subunit of RNA polymerase II and provide a link between transcription and pre-mRNA splicing. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2009]

SCAF4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30189973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAF4	NM_020706.2 linkuse as main transcript	c.3129C>G	p.His1043Gln	missense_variant	20/20	ENST00000286835.12	NP_065757.1	O95104-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SCAF4	ENST00000286835.12 linkuse as main transcript	c.3129C>G	p.His1043Gln	missense_variant	20/20	1	NM_020706.2	ENSP00000286835.7	O95104-1
SCAF4	ENST00000434667.3 linkuse as main transcript	c.3084C>G	p.His1028Gln	missense_variant	19/19	1		ENSP00000402377.2	O95104-3
SCAF4	ENST00000399804.5 linkuse as main transcript	c.3063C>G	p.His1021Gln	missense_variant	20/20	1		ENSP00000382703.1	O95104-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461824

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727224

show subpopulations

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2023

The c.3129C>G (p.H1043Q) alteration is located in exon 20 (coding exon 20) of the SCAF4 gene. This alteration results from a C to G substitution at nucleotide position 3129, causing the histidine (H) at amino acid position 1043 to be replaced by a glutamine (Q). 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

0.18

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;.;.

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.0065

MetaRNN

Benign

0.30

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.;.

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.2

D;D;D

REVEL

Benign

0.15

Sift

Uncertain

0.0020

D;D;D

Sift4G

Benign

0.32

T;T;T

Polyphen

1.0

D;B;.

Vest4

0.45

MutPred

0.25

Gain of helix (P = 0.132);.;.;

MVP

0.55

MPC

0.24

ClinPred

0.90

GERP RS

5.0

Varity_R

0.49

gMVP

0.067

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