Variant 6-154810101-G-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_014892.5(SCAF8):c.1313G>A(p.Arg438Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,724 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: 6.8e-7 ( 0 hom. )

Consequence

SCAF8
NM_014892.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.14

Variant links:

Genes affected

SCAF8 (HGNC:20959): (SR-related CTD associated factor 8) Enables RNA binding activity and RNA polymerase II C-terminal domain phosphoserine binding activity. Involved in negative regulation of termination of RNA polymerase II transcription, poly(A)-coupled and positive regulation of DNA-templated transcription, elongation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SCAF8 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=0.15715969).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAF8	NM_014892.5 linkuse as main transcript	c.1313G>A	p.Arg438Lys	missense_variant	12/20	ENST00000367178.8	NP_055707.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAF8	ENST00000367178.8 linkuse as main transcript	c.1313G>A	p.Arg438Lys	missense_variant	12/20	2	NM_014892.5	ENSP00000356146	P1	Q9UPN6-1
SCAF8	ENST00000417268.3 linkuse as main transcript	c.1547G>A	p.Arg516Lys	missense_variant	13/21	2		ENSP00000413098
SCAF8	ENST00000367186.7 linkuse as main transcript	c.1511G>A	p.Arg504Lys	missense_variant	14/22	2		ENSP00000356154		Q9UPN6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461724

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727158

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:

8.99e-7

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

Jun 22, 2023

The c.1313G>A (p.R438K) alteration is located in exon 12 (coding exon 12) of the SCAF8 gene. This alteration results from a G to A substitution at nucleotide position 1313, causing the arginine (R) at amino acid position 438 to be replaced by a lysine (K). 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

Pathogenic

0.63

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.080

T;.;T

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-2.0

N;N;.

REVEL

Benign

0.10

Sift

Benign

0.13

T;T;.

Sift4G

Benign

0.11

T;T;T

Polyphen

0.0030

B;.;.

Vest4

0.52

MutPred

0.24

.;Gain of methylation at R504 (P = 0.0129);.;

MVP

0.32

MPC

0.71

ClinPred

0.87

GERP RS

5.0

Varity_R

0.16

gMVP

0.50

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

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