rs1325252688

Variant names:

• chr6-154805452-G-C
• rs1325252688
• NM_014892.5:c.947G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014892.5(SCAF8):​c.947G>C​(p.Arg316Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: SCAF8 NM_014892.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.63
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37171465).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAF8	NM_014892.5	MANE Select	c.947G>C	p.Arg316Thr	missense	Exon 9 of 20	NP_055707.3
	SCAF8	NM_001286188.1		c.1181G>C	p.Arg394Thr	missense	Exon 10 of 21	NP_001273117.1	Q9UPN6
	SCAF8	NM_001286189.1		c.1145G>C	p.Arg382Thr	missense	Exon 11 of 22	NP_001273118.1	Q9UPN6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAF8	ENST00000367178.8	TSL:2 MANE Select	c.947G>C	p.Arg316Thr	missense	Exon 9 of 20	ENSP00000356146.3	Q9UPN6-1
	SCAF8	ENST00000417268.3	TSL:2	c.1181G>C	p.Arg394Thr	missense	Exon 10 of 21	ENSP00000413098.2	A0A0A0MT33
	SCAF8	ENST00000367186.7	TSL:2	c.1145G>C	p.Arg382Thr	missense	Exon 11 of 22	ENSP00000356154.4	Q9UPN6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 250952 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.089	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L
PhyloP100		6.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.27
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.080	T
Polyphen		0.98	D
Vest4		0.61
MutPred		0.37		Loss of stability (P = 0.3044)
MVP		0.21
MPC		1.0
ClinPred		0.69	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.32
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs1325252688; hg19: chr6-155126586;