chr6-154808160-C-T

Variant names:

• chr6-154808160-C-T
• rs766044209
• NM_014892.5:c.1072C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014892.5(SCAF8):​c.1072C>T​(p.Pro358Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SCAF8 NM_014892.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.24
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06181249).

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.1072C>T	p.Pro358Ser	missense	Exon 10 of 20	NP_055707.3
	SCAF8	NM_001286188.1		c.1306C>T	p.Pro436Ser	missense	Exon 11 of 21	NP_001273117.1	Q9UPN6
	SCAF8	NM_001286189.1		c.1270C>T	p.Pro424Ser	missense	Exon 12 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.1072C>T	p.Pro358Ser	missense	Exon 10 of 20	ENSP00000356146.3	Q9UPN6-1
	SCAF8	ENST00000417268.3	TSL:2	c.1306C>T	p.Pro436Ser	missense	Exon 11 of 21	ENSP00000413098.2	A0A0A0MT33
	SCAF8	ENST00000367186.7	TSL:2	c.1270C>T	p.Pro424Ser	missense	Exon 12 of 22	ENSP00000356154.4	Q9UPN6-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251234 AF XY: 0.0000147

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: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1461584 Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11 AN XY: 727128

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1111764

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74350

African (AFR) AF: 0.0000241 AC: 1 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000508 Hom.: 0

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	Benign	0.085
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.21
Eigen_PC	Benign	0.049
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.2
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.036
Sift	Benign	0.33	T
Sift4G	Benign	0.51	T
Polyphen		0.0050	B
Vest4		0.087
MutPred		0.28		Loss of loop (P = 0.0203)
MVP		0.10
MPC		0.71
ClinPred		0.16	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.054
gMVP		0.40
Mutation Taster		=93/7	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: rs766044209; hg19: chr6-155129294;