chr6-154795075-A-G

Variant names:

• chr6-154795075-A-G
• rs750401445
• NM_014892.5:c.542A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014892.5(SCAF8):​c.542A>G​(p.Gln181Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,461,098 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: SCAF8 NM_014892.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.25

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAF8	NM_014892.5	c.542A>G	p.Gln181Arg	missense_variant	Exon 6 of 20	ENST00000367178.8	NP_055707.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAF8	ENST00000367178.8	c.542A>G	p.Gln181Arg	missense_variant	Exon 6 of 20	2	NM_014892.5	ENSP00000356146.3
SCAF8	ENST00000417268.3	c.776A>G	p.Gln259Arg	missense_variant	Exon 7 of 21	2		ENSP00000413098.2
SCAF8	ENST00000367186.7	c.740A>G	p.Gln247Arg	missense_variant	Exon 8 of 22	2		ENSP00000356154.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000159 AC: 4 AN: 251078 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135740

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 SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1461098 Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11 AN XY: 726910

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: 0.000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.542A>G (p.Q181R) alteration is located in exon 6 (coding exon 6) of the SCAF8 gene. This alteration results from a A to G substitution at nucleotide position 542, causing the glutamine (Q) at amino acid position 181 to be replaced by an arginine (R). 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	Uncertain	0.39
BayesDel_addAF	Benign	0.000019	T
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;.;T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.6	M;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.7	D;D;.
REVEL	Uncertain	0.38
Sift	Uncertain	0.0030	D;D;.
Sift4G	Uncertain	0.030	D;D;D
Polyphen		0.98	D;.;.
Vest4		0.84
MutPred		0.32		.;Gain of solvent accessibility (P = 0.0411);.;
MVP		0.58
MPC		0.76
ClinPred		0.86	D
GERP RS		4.7
Varity_R		0.54
gMVP		0.73

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

LitVar

Other links and lift over

dbSNP: rs750401445; hg19: chr6-155116209;