Genetic Variant SCAF8:p.Asn169Ser (chr6-154795039-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014892.5(SCAF8):c.506A>G(p.Asn169Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000509 in 1,610,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

SCAF8
NM_014892.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.80

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.092050254).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014892.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCAF8	NM_014892.5	MANE Select	c.506A>G	p.Asn169Ser	missense	Exon 6 of 20	NP_055707.3
SCAF8	NM_001286188.1		c.740A>G	p.Asn247Ser	missense	Exon 7 of 21	NP_001273117.1	Q9UPN6
SCAF8	NM_001286189.1		c.704A>G	p.Asn235Ser	missense	Exon 8 of 22	NP_001273118.1	Q9UPN6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCAF8	ENST00000367178.8	TSL:2 MANE Select	c.506A>G	p.Asn169Ser	missense	Exon 6 of 20	ENSP00000356146.3	Q9UPN6-1
SCAF8	ENST00000417268.3	TSL:2	c.740A>G	p.Asn247Ser	missense	Exon 7 of 21	ENSP00000413098.2	A0A0A0MT33
SCAF8	ENST00000367186.7	TSL:2	c.704A>G	p.Asn235Ser	missense	Exon 8 of 22	ENSP00000356154.4	Q9UPN6-2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000444

AC:

AN:

247550

AF XY:

0.0000448

show subpopulations

Gnomad AFR exome

AF:

0.0000624

Gnomad AMR exome

AF:

0.0000597

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000444

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000432

AC:

AN:

1458580

Hom.:

Cov.:

AF XY:

0.0000469

AC XY:

AN XY:

725626

show subpopulations

African (AFR)

AF:

0.000150

AC:

AN:

33234

American (AMR)

AF:

0.0000682

AC:

AN:

43976

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26058

East Asian (EAS)

AF:

0.0000507

AC:

AN:

39458

South Asian (SAS)

AF:

0.000105

AC:

AN:

85546

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0000315

AC:

AN:

1110926

Other (OTH)

AF:

0.000116

AC:

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000125

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41546

American (AMR)

AF:

0.0000654

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000291

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000110

EpiControl

AF:

0.0000598

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.018

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.042

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.011

MetaRNN

Benign

0.092

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

5.8

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.56

REVEL

Benign

0.063

Sift

Benign

0.084

Sift4G

Benign

0.69

Polyphen

0.063

Vest4

0.36

MVP

0.26

MPC

0.56

ClinPred

0.065

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.058

gMVP

0.47

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over