rs756760142

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014892.5(SCAF8):c.3151C>G(p.Arg1051Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,704 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1051W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

SCAF8
NM_014892.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82

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:

TIAM2 (HGNC:11806): (TIAM Rac1 associated GEF 2) This gene encodes a guanine nucleotide exchange factor. A highly similar mouse protein specifically activates ras-related C3 botulinum substrate 1, converting this Rho-like guanosine triphosphatase (GTPase) from a guanosine diphosphate-bound inactive state to a guanosine triphosphate-bound active state. The encoded protein may play a role in neural cell development. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

TIAM2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14130422).

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.3151C>G	p.Arg1051Gly	missense	Exon 20 of 20	NP_055707.3
SCAF8	NM_001286188.1		c.3385C>G	p.Arg1129Gly	missense	Exon 21 of 21	NP_001273117.1	Q9UPN6
SCAF8	NM_001286189.1		c.3349C>G	p.Arg1117Gly	missense	Exon 22 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.3151C>G	p.Arg1051Gly	missense	Exon 20 of 20	ENSP00000356146.3	Q9UPN6-1
SCAF8	ENST00000417268.3	TSL:2	c.3385C>G	p.Arg1129Gly	missense	Exon 21 of 21	ENSP00000413098.2	A0A0A0MT33
SCAF8	ENST00000367186.7	TSL:2	c.3349C>G	p.Arg1117Gly	missense	Exon 22 of 22	ENSP00000356154.4	Q9UPN6-2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151904

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000799

AC:

AN:

250376

AF XY:

0.00000738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727200

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000243

AC:

AN:

1111954

Other (OTH)

AF:

0.0000331

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

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:

0.00000658

AC:

AN:

151904

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74152

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41360

American (AMR)

AF:

0.00

AC:

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

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:

0.0000154

Hom.:

Bravo

AF:

0.00000756

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

Pathogenic

0.61

BayesDel_addAF

Uncertain

0.082

BayesDel_noAF

Benign

-0.12

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.053

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.0

PhyloP100

1.8

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-1.9

REVEL

Benign

0.25

Sift

Uncertain

0.0050

Sift4G

Benign

0.48

Polyphen

1.0

Vest4

0.42

MutPred

0.18

Loss of methylation at R1117 (P = 0.0286)

MVP

0.15

MPC

0.37

ClinPred

0.62

GERP RS

3.2

PromoterAI

-0.049

Neutral

(source)

Varity_R

0.35

gMVP

0.50

Mutation Taster

=93/7

polymorphism

(source)

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

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